Hormonal Effects on External Genitalia

by Peter Ward, PhD

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    00:01 Now, development of the external genitalia is strictly regulated and controlled by various hormonal signals.

    00:08 Testis-determining factor is going to promote the formation of testosterone by Laydig cells between days 50 and 150.

    00:16 At this time, testosterone is converted by 5alpha-reductase to the very powerful Dihydrotestosterone or DHT.

    00:24 The DHT spike that occurs between days 50 and 150 is going to be what promotes the formation of male internal and external genitalia and the appearance of it as a penis and scrotum.

    00:37 A second spike in testosterone production at puberty, not a DHT spike but just testosterone, is what causes stereotypical male secondary sexual characteristics to come into existence.

    00:50 So expansion of the thyroid cartilage, deepening of the voice, and so forth, will be due to that pubertal spike in testosterone.

    00:58 This is also what allows the seminiferous tubules of the testis to develop a canal or a lumen which can then carry spermatozoa from the testis to the urethra.

    01:09 Now, another thing that can happen with testosterone is that it can be converted to estrogen by another enzyme called aromatase.

    01:17 This is important in both sexes because the placenta produces a great deal of testosterone and it’s not uncommon for women to develop hair growth during pregnancy if they’re getting exposed to too much testosterone from the placenta.

    01:33 Increased exposure to estrogen at puberty is going to be what drives the formation of feminine secondary sexual characteristics such as breast development.

    01:42 The proportion of testosterone and estrogen that a person is exposed to both in the womb and at the puberty is going to be what drives masculine or feminine development.

    01:53 And it’s not uncommon for pubescent boys who are producing a great deal of testosterone, some of which develops into estrogen, to develop gynecomastia or breast tissue that later regresses as the level of hormone exposure drops.

    02:06 Ambiguous genitalia occur when either a clitoris in a female newborn is enlarged or a penis in a male newborn is decreased in size with possible hypospadias.

    02:19 These phenotypes appear different from the genotype.

    02:24 Meaning, you can be XX, chromosomally female but develop male sexual characteristics or XY, genetically male but developing female secondary sexual characteristics.

    02:36 There are some children who are XY with mutations that affect the production of DHT.

    02:41 You’ll recall that DHT is important to signal masculine development in the womb.

    02:46 In the case of these children, they will develop in stereotypically, female looking ways until puberty when the testosterone spike that’s produced at that time will kick start masculine secondary structural characteristic development.

    03:01 There are also female pseudohermaphrodites who are genetically female with two X chromosomes but have a masculine appearance and masculine secondary sexual characteristics.

    03:11 This is due to increased levels of testosterone exposure while they’re developing in the womb.

    03:16 This may be due to the aromatase enzyme being mutated and not converting that testosterone into estrogen.

    03:22 The enlarged clitoris in these people is going to resemble a penis and the labia majora may be enlarged and even fused to a variable degree resembling a scrotum.

    03:34 However, because you need the Y chromosome and its testis-determining factor to prevent formation of the uterine tubes, uterus, and other internal female genitalia, the paramesonephric ducts will still be present and will form a rudimentary or even relatively stout uterus and oviduct.

    03:56 Male pseudohermaphrodites are those who are XY in their genotype and would otherwise develop as males but have a feminine appearance.

    04:06 This is often due to mutation in the enzyme that senses and responds to androgens, testosterone, and DHT.

    04:14 In this case, the testis are small and relatively undeveloped.

    04:18 They don’t descend into the scrotum and in fact, the labioscrotal swellings often remain separate, similar to a labia majora.

    04:26 The penis will not enlarge and may appear clitoris like.

    04:29 So testis-determining factor is still present.

    04:32 It’s still there being produced by the Y chromosome, so paramesonephric ducts will not form and only a short vagina may be present developing off of the urogenital sinus.

    04:43 People with this condition appear hyper-feminine because unlike women who have receptors for both hormones, these people have no response to testosterone of any kind and they typically grow up as women, believe themselves to be women, both genetically and phenotypically and are often undiagnosed until they attempt to have children and find that there is no uterus or oviduct present within their body.

    05:07 Another cause of difficulty in sexual development is congenital adrenal hyperplasia.

    05:14 This is caused by mutations and just various genes that regulate hormone production in the adrenal gland, specifically, the adrenal cortex.

    05:22 It can be caused by conversion of cholesterol which produces all of our hormones into sex hormones.

    05:29 This can cause ambiguous genitalia in female infants where the clitoris and other external genitalia enlarge but no notable signs in male infants.

    05:38 Precocious puberty can occur in both cases since excessive levels of hormones are present.

    05:44 Less common forms of congenital adrenal hyperplasia can actually cause excessive but faulty sex hormone expression that results in the opposite, ambiguous male genitalia and no immediate effects in female infants.

    05:57 True hermaphrodites, those with both male and female internal genitalia are incredibly rare in humans.

    06:05 Thank you very much for your attention and I hope to see you on our next talk.

    About the Lecture

    The lecture Hormonal Effects on External Genitalia by Peter Ward, PhD is from the course Development of the Abdominopelvic Region. It contains the following chapters:

    • Hormonal Effects on External Genitalia
    • Ambiguous Genitalia and Hermaphrodites
    • Congenital Adrenal Hyperplasia

    Included Quiz Questions

    1. Aromatase converts testosterone to estrogen.
    2. Aromatase converts estrogen to testosterone.
    3. Aromatase converts testosterone to dihydrotestosterone.
    4. Aromatase induces the secondary hormone spike during puberty in males.
    5. Aromatase stimulates the production of 5-alpha-reductase.
    1. Development in a feminine manner until puberty when testosterone spike promotes masculine secondary sexual characteristics
    2. Development in a masculine manner until puberty when DHT is unable to promote secondary sexual characteristic development
    3. Development with ambiguous genitalia until puberty when female secondary sexual characteristics predominate
    4. Development with variable degree primary sexual characteristics but paramesonephric ducts remain and form internal female organs
    5. Typically these patients grow up with a hyper-feminine appearance and are unaware of their chromosomal sex until attempting to have children
    1. CAH results in ambiguous genitalia in male infants.
    2. CAH results from mutations in various genes, regulating hormone formation in the adrenal cortex.
    3. CAH is caused by excessive conversion of cholesterol to sex hormones.
    4. CAH may result in ambiguous genitalia in female infants.
    5. CAH may result in precocious puberty in both males and females.

    Author of lecture Hormonal Effects on External Genitalia

     Peter Ward, PhD

    Peter Ward, PhD

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