Hormonas Gonadais

Descrição Geral

Definição

Hormonas Gonadais:

As hormonas gonadais são produzidas pelas gónadas humanas: testículos e ovários. Estas hormonas incluem:

• Androgénios, incluindo a testosterona.
• Estrogénios
• Progestinas

Terminologia de género:

Reconhecendo a complexidade e a natureza delicada em torno da terminologia de género, para os propósitos deste documento:

• Os autores reconhecem que existe um espectro (e não uma divisão binária) de identidades de género, órgãos sexuais e caracteres sexuais secundários.
• “Feminino” será utilizado para descrever:
  • Hormonas estrogénicas
  • Indivíduos com ovários que produzem naturalmente maiores quantidades de estrogénios do que de androgénios
• “Masculino” será utilizado para descrever:
  • Hormonas androgénicas
  • Indivíduos com testículos que produzem naturalmente maiores quantidades de androgénios do que de estrogénios

Eixo hipotálamo-hipófise-gonadal (HHG)

As hormonas secretadas pelas gónadas são estimuladas pelo eixo hipotálamo-hipófise-testiculo (HHT) nos homens e pelo eixo hipotálamo-hipófise-ovário (HPO) nas mulheres, ajudando na regulação destes mesmos eixos.

• Hipotálamo:
  • Hormona libertadora de gonadotrofinas (GnRH)
  • A GnRH é secretada pelos núcleos pré-óticos (principais) e supraóticos.
• Hipófise:
  • A GnRH estimula as células gonadotróficas da hipófise a secretar a hormona folículo-estimulante ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle) e a hormona luteinizante ( LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle).
  • FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle: estimula o desenvolvimento dos gâmetas
  • LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle:
    • Estimula a produção de androgénios em ambos os sexos
    • O pico de LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle desencadeia a ovulação nas mulheres
• Gónadas: produzem e secretam as hormonas gonadais:
  • Testosterona
  • Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins
  • Progesterona
• Produção de GnRH e FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle/ LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle é regulada por:
  • Hormonas produzidas a nível das gónadas
  • Stress (sobretudo desnutrição crónica e exercício físico excessivo)

Via da síntese hormonal sexual

Todas as hormonas gonadais são esteroides, produzidas a partir do colesterol através de uma série de passos enzimáticos. Os passos da via metabólica das hormonas sexuais incluem:

• Colesterol →
• Pregnenolona →
• Progesterona →
• 17α-hidroxiprogesterona (17α-OHP) →
• Androstenediona, que pode ser convertida em →
• Testosterona ou estrona ( E1 E1 An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from androstenedione directly, or from testosterone via estradiol. In humans, it is produced primarily by the cyclic ovaries, placenta, and the adipose tissue of men and postmenopausal women. Noncontraceptive Estrogen and Progestins), ambas podem ser convertidas em →
• Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins (E2)

Transporte das hormonas gonadais na circulação sanguínea

Derivadas do colesterol, as hormonas gonadais são lipofílicas, pelo que têm de estar ligadas a proteínas para circular no sangue. Geralmente, estão ligadas a:

• Globulina de ligação a hormonas sexuais ( SHBG SHBG A glycoprotein migrating as a beta-globulin. Its molecular weight, 52, 000 or 95, 000-115, 000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Gonadal Hormones): cerca de 40%
• Outras proteínas (principalmente albumina e globulina de ligação aos corticosteróides): cerca de 54%-60%
• Hormona livre (a única forma ativa biologicamente): cerca de 2%.

Recetores hormonais gonadais

• As hormonasgonadais são lipofílicas → conseguem atravessar livremente as membranas celulares para se ligar aos recetores intracelulares.
• Uma vez ligadas aos recetores → translocação para o núcleo
• O complexo hormona-recetor pode ligar-se ao DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure e afetar assim a expressão genética.

Endocrinologia Reprodutiva Masculina

Anatomia dos túbulos seminíferos

• O esperma desenvolve-se nos túbulos seminíferos dos testículos
• Os túbulos incluem 2 células principais estromais do cordão sexual:
  • Células de Leydig: sintetizam testosterona
  • Células de Sertoli: revestimento interno dos túbulos

Visão geral do eixo hipotalámo-hipófise-testículo

• Os neurónios pré-óticos no hipotálamo secretam GnRH.
• A GnRH estimula a hipófise anterior a libertar:
  • LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
  • FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
• A LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle e a FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle estimulam as células nos testículos:
  • LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle: afeta principalmente as células de Leydig → estimula a produção de testosterona
  • FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle: afeta principalmente as células do Sertoli:
    • Estimula a espermatogénese
    • Sinttetiza péptidos reguladores (incluindo inibina) e vários fatores de crescimento
• Alguma testosterona é convertida em:
  • Dihidrotestosterona ( DHT DHT A potent androgenic metabolite of testosterone. It is produced by the action of the enzyme 3-oxo-5-alpha-steroid 4-dehydrogenase. Gonadal Hormones): via 5α-reductase
  • 17-cetosteroides
  • Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins:
    • Via aromatase Aromatase An enzyme that catalyzes the desaturation (aromatization) of the ring a of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the cyp19 gene, and functions in complex with NADPH-ferrihemoprotein reductase in the cytochrome p450 system. Adipose Tissue: Histology presente nas células de Sertoli
    • Ajuda as células de Leydig a produzir mais MAIS Androgen Insensitivity Syndrome testosterona
• Feedback e regulação do eixo HHT:
  • Testosterona: inibe a secreção de GnRH, FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle e LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
  • Inibina: inibe a FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle de forma seletiva

Efeitos da LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle e da FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle nos testículos

• LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle:
  • Ativa a enzima de clivagem da cadeia lateral nas células de Leydig, que inicia a conversão do colesterol em testosterona.
  • A testosterona acumula-se nas células de Leydig → move-se para:
    • Células de Sertoli vizinhas
    • Corrente sanguínea sendo transportada para todo o corpo
• FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle:
  • Estimula a espermatogénese nas células de Sertoli
  • A espermatogénese requer a testosterona produzida pelas células de Leydig.

Efeitos da testosterona e de outros androgénios

A testosterona, e os outros androgénios, são responsáveis pelo desenvolvimento dos caracteres sexuais masculinos tanto primários como secundários.

• Estimula o crescimento dos órgãos reprodutores masculinos:
  • Aumento do pénis, dos testículos e do escroto
  • Desenvolvimento ductal e glandular do sistema reprodutivo masculino
• Estimula a espermatogénese; sem testosterona, os homens tornam-se inférteis
• Estimula o desenvolvimento dos caracteres sexuais secundários:
  • Pelos androgénicos:
    • Pelos púbicos
    • Pelos axilares
    • Pelos faciais (região da barba e bigode)
  • Alterações dermatológicas:
    • A pele torna-se mais MAIS Androgen Insensitivity Syndrome escura e espessa
    • ↑ Secreção sebácea → pode levar ao acne
    • ↑ Glândulas sudoríparas apócrinas
  • Crescimento da laringe → voz mais MAIS Androgen Insensitivity Syndrome grave
• Efeitos músculo-esqueléticos:
  • ↑ Crescimento ósseo
  • ↑ Massa muscular
  • ↑ Tecido conjuntivo

Secreção de testosterona ao longo da vida do homem

A secreção de testosterona varia ao longo da vida do homem:

• Níveis máximos:
  • In utero
  • Começa na puberdade e permanece ao longo da vida adulta
• Começa a diminuir por volta dos 60 anos
• A testosterona é secretada em pulsos ao longo do dia.

Endocrinologia Reprodutiva Feminina

Estrutura dos folículos em desenvolvimento

• O folículo em desenvolvimento é um pequeno quisto que se forma ao redor de cada oócito.
• Rodeado por 2 tipos de células estromais principais:
  • Células da granulosa
  • Células da teca
• As células do estroma produzem as hormonas gonadais nas mulheres.

Visão geral do eixo hipotálamo-hipófise-ovário

• Os neurónios pré-óticos no hipotálamo secretam GnRH de forma pulsátil.
• Os pulsos de GnRH, em conjunto com outros ritmos biológicos, acionam a hipófise anterior para libertar:
  • FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle:
    • Estimula o desenvolvimento folicular e a maturação do ovo
    • Estimula as células da granulosa no ovário a produzir E2
  • LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle:
    • Estimula as células da teca no ovário a produzir testosterona (a maior parte da qual é convertida em E2 nas células da granulosa)
    • Um pico de LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle no meio do ciclo desencadeia a ovulação
• Hormonas produzidas pelos ovários:
  • Estrogénios:
    • E2: principal estrogénio produzido em mulheres em idade reprodutiva
    • E1 E1 An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from androstenedione directly, or from testosterone via estradiol. In humans, it is produced primarily by the cyclic ovaries, placenta, and the adipose tissue of men and postmenopausal women. Noncontraceptive Estrogen and Progestins: estrogénio mais MAIS Androgen Insensitivity Syndrome fraco; principal estrogénio em mulheres na menopausa
    • Estriol Estriol A hydroxylated metabolite of estradiol or estrogen that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During pregnancy, a large amount of estriol is produced by the placenta. Isomers with inversion of the hydroxyl group or groups are called epiestriol. Noncontraceptive Estrogen and Progestins ( E3 E3 A hydroxylated metabolite of estradiol or estrogen that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During pregnancy, a large amount of estriol is produced by the placenta. Isomers with inversion of the hydroxyl group or groups are called epiestriol. Noncontraceptive Estrogen and Progestins): produzido principalmente durante a gravidez
  • Progestinas (produzidas em quantidades significativas apenas após a ovulação):
    • Progesterona
    • Compostos semelhantes à progesterona (por exemplo, 17α-OHP)
  • Inibinas
  • Ativinas
  • Androgénios
• Feedback e regulação do eixo HHO:
  • Os estrogénios e a progesterona, durante a maior parte do ciclo menstrual, inibem:
    • Secreção hipofisária da FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle e LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
    • Secreção hipotalámica da GnRH
    • Ou seja, durante a maior parte do ciclo menstrual, o estrogénio provoca feedback negativo na hipófise.
  • Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins a meio do ciclo:
    • Estimula a secreção hipofisária da FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle e LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → provoca um ↑ da produção de estrogénios → aumenta ainda mais MAIS Androgen Insensitivity Syndrome a secreção de FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle e LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
    • Ou seja, os estrogénios começam a provocar um feedback positivo na hipófise
    • Provoca um pico de LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → desencadeia a ovulação
  • Inibina: inibe a secreção FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle de forma seletiva
  • Ativina: estimula a secreção de LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle, especialmente a meio do ciclo

Pulsatilidade da gonadotrofina

A GnRH é libertada de uma forma pulsátil, seguindo múltiplos ritmos biológicos:

• Principais fases de crescimento e desenvolvimento (por exemplo, infância → puberdade → anos reprodutivos → menopausa)
• Ritmos circadianos: ciclos de 24 horas
• Ritmos ultradianos: ciclos de < 24 horas
• Ritmos infradianos: ciclos de > 24 horas (ritmos mensais)

Síntese de estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins e progesterona

Revisão da via metabólica das hormonas sexuais: colesterol → pregnenolona → progesterona → 17α-OHP → androstenediona → testosterona ou E1 E1 An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from androstenedione directly, or from testosterone via estradiol. In humans, it is produced primarily by the cyclic ovaries, placenta, and the adipose tissue of men and postmenopausal women. Noncontraceptive Estrogen and Progestins → E2

• Células da teca:
  • Contêm 17α-hidroxilase: converte progesterona em 17α-OHP
  • A 17α-OHP depois é convertida em testosterona
  • Estimuladas pela LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
• Células da granulosa:
  • Convertem colesterol → progesterona (não há 17α-hidroxilase presente nas células da granulosa para avançar na via até à testosterona)
  • Contém aromatase Aromatase An enzyme that catalyzes the desaturation (aromatization) of the ring a of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the cyp19 gene, and functions in complex with NADPH-ferrihemoprotein reductase in the cytochrome p450 system. Adipose Tissue: Histology:
    • Converte a testosterona produzida pelas células da teca → E2
    • Converte a androstenediona produzida pelas células da teca → E1 E1 An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from androstenedione directly, or from testosterone via estradiol. In humans, it is produced primarily by the cyclic ovaries, placenta, and the adipose tissue of men and postmenopausal women. Noncontraceptive Estrogen and Progestins
    • A aromatase Aromatase An enzyme that catalyzes the desaturation (aromatization) of the ring a of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the cyp19 gene, and functions in complex with NADPH-ferrihemoprotein reductase in the cytochrome p450 system. Adipose Tissue: Histology é estimulada pela FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
• Resultados finais:
  • As células da teca produzem testosterona (a maioria, mas não toda, é convertida em E2 nas células da granulosa).
  • As células da granulosa produzem:
    • Estrogénio
    • Progesterona

Efeitos dos estrogénios

Os estrogénios desempenham um papel crucial no desenvolvimento sexual das mulheres e no ciclo menstrual; no entanto, os estrogénios são responsáveis também por inúmeras funções não reprodutivas.

• Estimulam o crescimento dos órgãos reprodutivos femininos:
  • Responsáveis pela construção do endométrio durante o ciclo menstrual todos os meses
  • Crescimento do miométrio
  • ↑ Força/integridade do tecido vaginal
  • ↑ Lubrificação vaginal
  • ↑ Crescimento ovárico
• Mamas:
  • Estimula o desenvolvimento das mamas
  • ↓ Produção de leite
• Produzem a “aparência física feminina” devido à deposição de gordura nas:
  • Mamas
  • Ancas, nádegas e coxas
  • Grandes lábios e sínfise púbica
• Efeitos endócrinos:
  • Inibem a FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle e a GnRH → os estrogénios são agentes contracetivos eficazes
  • ↑ Recetores da LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle nas células da granulosa
• Efeitos ósseos:
  • Promove o crescimento ósseo:
    • Desencadeia o surto de crescimento na puberdade
    • A osteoporose torna-se um problema quando ocorre os níveis de E2 diminuem na menopausa
  • Encerramento das placas de crescimento
• Efeitos favoráveis sobre os perfis lipídicos
  • ↓ Colesterol total e LDL
  • ↑ HDL
  • Relevância clínica:
    • Mulheres em pré-menopausa têm ↓ risco cardiovascular em comparação com os homens da mesma idade
    • Na menopausa, ↓ E2 → ↑ risco cardiovascular
• ↑ Fatores de coagulação → o tromboembolismo é um dos riscos principais das terapêuticas com estrogénios

Efeitos das progestinas

O progesterona é produzida principalmente pelo corpo lúteo após a ovulação.

• Efeitos uterinos:
  • ↑ Secreções endometriais
  • Estabiliza e provoca maturação do endométrio na 2.ª metade do ciclo menstrual → prepara o endométrio para a implantação
  • Torna o muco cervical mais MAIS Androgen Insensitivity Syndrome espesso (um muco cervcial fino é necessário para o transporte dos espermatozoides para o útero)
  • A abstinência de progestina desencadeia a hemorragia menstrual.
• Efeitos mamários:
  • ↑ Glândulas lácteas → podem causar sensibilidade mamária que ocorre durante a menstruação
  • ↓ Produção de leite → suprime a lactação durante a gravidez
• ↑ Temperatura corporal basal → pode ser usado para rastreio da ovulação
• Necessárias para o desenvolvimento da placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity durante a gravidez

Resumo da Comparação: Homem versus Mulher

Relevância Clínica

• Contracetivos hormonais: contêm uma combinação de etinilestradiol e progestina ou progestina isoladamente. Estas hormonas sintéticas comportam riscos cardiovasculares ligeiramente superiores ao estradiol e à progesterona, mas têm melhores efeitos contracetivos. Os contracetivos hormonais estão disponíveis sob muitas formas (por exemplo, pílulas, dispositivos intrauterinos). Por um lado inibem a libertação de FSH (prevenindo o desenvolvimento folicular), e, por outro lado, as progestinas suprimem o desenvolvimento endometrial e a produção de muco cervical.
• Terapêutica de substituição hormonal (TSH): tipicamente à base de estradiol e progesterona “bioidênticos” (em vez de estrogénios e progestativos sintéticos) devido à melhoria dos perfis de segurança. A TSH é indicada em indivíduos que sofrem de sintomas causados pelas flutuações hormonais e queda dos níveis hormonais na menopausa (por exemplo, afrontamentos, oscilações de humor). Outras indicações incluem insuficiência ovárica primária (ou seja, menopausa precoce), hipogonadismo masculino e disforia de género.
• Hipogonadismo: condição caracterizada pela produção reduzida, ou ausente, de hormonas sexuais pelos testículos, ou ovários. O hipogonadismo pode ser devido a falha ao nível das gónadas ou devido a defeitos nas secreções hipotalámicas, ou hipofisárias estimulantes. Os achados incluem infertilidade, aumento do risco de osteoporose, disfunção eréctil, diminuição da libido e regressão (ou ausência) dos caracteres sexuais secundários. O diagnóstico requer a colheita de história clínica, exame físico e exames laboratoriais. O tratamento é com terapêutica de substituição hormonal.
• Insuficiência ovariana primária (IOP): anteriormente referida como “insuficiência ovárica precoce”, IOP inclui casos de menopausa precoce, com cessação da ovulação e menstruação antes dos 40 anos. O tratamento requer TSH para prevenir a osteoporose precoce e doenças cardiovasculares. As preocupações com a fertilidade também devem ser abordadas tal TAL Renal Sodium and Water Regulation como desejado pela pessoa em causa.
• Ginecomastia: proliferação benigna do tecido glandular e ductal mamário masculino. As causas podem ser fisiológicas (devido a desequilíbrios nos estrogénios e androgénios que ocorrem mais MAIS Androgen Insensitivity Syndrome frequentemente em recém-nascidos, na puberdade e nos idosos) ou podem ser devidas a fármacos, cirrose, DRC, hipogonadismo, hipertiroidismo, desnutrição e neoplasias testiculares. Quando presente nos homens, deve ser feito diagnóstico diferencial com cancro da mama.