Pituitary Gland

The pituitary gland, also known as the hypophysis, is considered the “master endocrine gland” because it releases hormones that regulate the activity of multiple major endocrine organs in the body. The gland sits on the sella turcica, just below the hypothalamus, which is the primary regulator of the pituitary gland. The pituitary gland has 2 lobes: the anterior lobe (the adenohypophysis) and the posterior lobe (the neurohypophysis). Each lobe has its own regulation, set of secretory products, and feedback loops. Abnormalities in the pituitary gland can lead to a wide range of clinical conditions, some of which include hyperprolactinemia, acromegaly, hyperthyroidism or hypothyroidism, and central diabetes insipidus.

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Overview

The pituitary gland is known as the “master endocrine gland.” This gland receives stimulatory input from the hypothalamus and secretes multiple different hormones, which target multiple different end organs and have wide-ranging effects throughout the body.

Location

  • Located in the sella turcica of the sphenoid bone
  • Just below the optic chiasm
  • Connected to the hypothalamus by the pituitary stalk 
  • Lies outside the dura
Hypothalamic–pituitary complex

Hypothalamic–pituitary complex:
The image shows the pituitary gland, made up of the anterior and posterior lobes, in relation to the hypothalamus.

Image: “1806 The Hypothalamus-Pituitary Complex” by OpenStax College. License: CC BY 3.0

General structure

The pituitary gland is divided into 2 primary components: 

  • Adenohypophysis (also known as the anterior pituitary) 
  • Neurohypophysis (also known as the posterior pituitary)

The 2 halves function independently, as 2 separate glands, each with their own:

  • Embryologic origins
  • Anatomy
  • Connections to the hypothalamus
  • Regulatory controls
  • Functions

Development and Gross Anatomy

Development

Anterior pituitary:

  • Develops from outpocket of the oropharynx (Rathke pouch)
  • Derived from oral ectoderm 

Posterior pituitary:

  • Downgrowth from the 3rd ventricle of the brain 
  • Derived from neuroectoderm

Gross anatomy

Major components of the pituitary gland include:

  • Pars distalis: the bulk of the glandular portion/anterior pituitary
  • Pars nervosa: the bulk of the neurosecretory portion/posterior pituitary
  • Pars intermedia: a thin wedge separating the pars distalis from the pars nervosa
  • Pituitary stalk:
    • Connects the pea-like lobes of the pituitary (the pars distalis and the pars nervosa) to the hypothalamus
    • Consists of: 
      • Infundibulum: arises from the posterior pars nervosa
      • Pars tuberalis: arises from the anterior pars distalis and wraps around the infundibulum
Major subdivisions of the pituitary gland hypophysis

Major subdivisions of the pituitary gland (hypophysis)

Image by Lecturio.

Connection to the hypothalamus

Adenohypophysis/anterior pituitary: via the hypothalamohypophysial portal system (i.e., connected via the circulation): 

  1. Hormones are secreted by neurosecretory cells within the median eminence of the hypothalamus.
  2. Hormones enter the primary capillary plexus of the portal system in the hypothalamus.
  3. Primary capillary plexus drains into venules known as portal veins.
  4. Portal veins carry these regulatory hormones down the pars tuberalis to the anterior pituitary.
  5. A secondary capillary plexus surrounds the anterior pituitary cells.
  6. Regulatory hormones leave the portal system and act on their target cells in the anterior pituitary.
  7. Cells within the anterior pituitary release their hormones into the circulation. 
  8. Pituitary hormones are taken up by the surrounding veins and travel to peripheral target organs.

Neurohypophysis/posterior pituitary: via the hypothalamohypophysial tract (i.e., directly connected via the nerves)

  • Hormones are synthesized within the hypothalamic nuclei:
    • Paraventricular nuclei: oxytocin
    • Supraoptic nuclei: antidiuretic hormone (ADH)
  • Hormones travel down the neuronal axons in the infundibulum in the pituitary stalk and are stored in the axon terminals.
  • Axon terminals are located within the posterior pituitary.
  • When the hypothalamus is stimulated, the signal travels down the axons in the hypothalamohypophysial tract → triggers release of the stored hormones directly into circulation within the posterior pituitary
  • Note: The posterior pituitary can be thought of as an extension of the hypothalamus.

Microscopic Anatomy

Adenohypophysis (anterior pituitary)

General characteristics:

  • Glandular portion of the pituitary
  • Consists of endocrine cells and dense capillary networks
  • Categorization:
    • The endocrine cells can be categorized as chromophils or chromophobes, based on staining characteristics. 
    • Specific cell types can be differentiated by immunocytochemical staining.
  • Endocrine cells get their stimulation from hypothalamic hormones secreted into the primary capillaries of the hypothalamohypophysial portal system.

Chromophils:

  • Basophils: 
    • Corticotropes: 
      • Release adrenocorticotropic hormone (ACTH) 
      • 15%–20% of endocrine cells
    • Thyrotropes: 
      • Release thyroid-stimulating hormone (TSH)
      • 5% of endocrine cells
    • Gonadotropes: 
      • Release luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
      • 10% of endocrine cells
  • Acidophils: 
    • Lactotropes: 
      • Release prolactin
      • 15%–20% of endocrine cells 
    • Somatotropes: 
      • Release growth hormone (GH)
      • 50% of endocrine cells

Chromophobes:

  • Cells that do not take up stain well
  • Function is unclear.
Microanatomy Histology_of_pars_distalis_of_the_anterior_pituitary_with_chromophobes

Microanatomy of the pars distalis in the anterior lobe of the pituitary gland showing chromophobes, basophils, and acidophils

Image: “Microanatomy of the pars distalis showing chromophobes, basophils, and acidophils” by Mikael Häggström. License: CC0 1.0

Neurohypophysis (posterior pituitary)

The neurohypophysis is filled with the terminal axons of neurosecretory cells, supporting cells known as pituicytes, and dense networks of fenestrated capillaries.

  • Neurosecretory cells (nerve cells):
    • Cell bodies are within the hypothalamus.
    • Unmyelinated axons travel down the pituitary stalk.
    • Axon terminals are located within the posterior pituitary.
  • Herring bodies: 
    • The axon terminals containing vesicles of stored secretory products (oxytocin and ADH) waiting to be released
    • Appear histologically as eosinophilic swellings
  • Pituicytes: 
    • Nerve cells similar to astrocytes found in the CNS
    • Supporting cells that wrap around the axons and capillary vessels
    • Maintain the integrity of the blood–brain barrier
    • Assist in regulating hormone release from the axons

Vasculature

Arterial supply

  • Superior hypophysial artery:
    • Supplies the primary capillary plexus in the median eminence of the hypothalamus (forms the 1st part of the hypothalamohypophysial portal system)
    • Originates from the internal carotid artery
  • Trabecular artery: connects the superior and inferior hypophysial arteries
  • Inferior hypophysial artery: 
    • The major arterial supply for the posterior pituitary
    • Originates from the meningohypophysial trunk (a branch of the internal carotid artery)
    • Fenestrated capillaries → allow for hormones secreted in the posterior pituitary to easily enter systemic circulation
    • Note: The anterior pituitary lacks a direct major arterial supply → gets its supply from the portal system capillary network

Venous drainage

Both the anterior and posterior pituitary drain into:

  • Hypophysial veins, which drain into:
    • Cavernous sinus → petrosal sinuses → internal jugular veins

Functions

The pituitary gland’s primary function is to secrete a variety of regulatory hormones.

Anterior pituitary hormones

Hormones secreted by the anterior pituitary affect many of the other major endocrine glands in the body. Hormones are part of complex regulatory systems known as “axes.” These axes are summarized in the table below.

Table: Hypothalamic-pituitary axis (HPA) hormones and targets
Hypothalamic hormonePituitary target cellPituitary hormoneTarget organEnd effects
Corticotropin-releasing hormone (CRH)CorticotropesACTHAdrenal cortexRelease of corticosteroids
Thyrotropin-releasing hormone (TRH)ThyrotropesTSHThyroid glandRelease of thyroid hormones
Gonadotropin-releasing hormone (GnRH)GonadotropesFSH
  • Gonads
  • Ovaries
  • Testes
Development of ovarian follicles and sperm production
LH
  • Gonads
  • Ovaries
  • Testes
  • Androgen production (both sexes)
  • Stimulates ovulation (females)
Growth hormone–releasing hormone (GHRH)SomatotropesGHMany organsAnabolic effects
Somatostatin (inhibitor)SomatotropesGH (inhibited)Many organsAnabolic effects inhibited with somatostatin
Dopamine (inhibitor)LactotropesProlactin (inhibited)Mammary glandsMilk production inhibited with dopamine

Posterior pituitary hormones

The 2 major posterior pituitary hormones are ADH and oxytocin, which are not involved in regulatory axes the way the anterior pituitary hormones are. These hormones act directly on end target organs.

Table: Hormones of posterior pituitary
HormoneSynthesisTarget organFunction
Antidiuretic hormone (ADH)Supraoptic nuclei of hypothalamusKidney
  • Water reabsorption from kidney
  • Vasoconstriction
  • Increase blood pressure
OxytocinParaventricular nuclei of hypothalamusBreastStimulates milk ejection during lactation
UterusStimulates uterine contractions during labor

Clinical Relevance

  • Hypopituitarism: condition characterized by a deficiency of all the pituitary hormones. Because these hormones regulate multiple different organs, the effects of pituitary hypofunction are multisystemic. Causes include pituitary masses, congenital syndromes, trauma, infections, and vascular damage. Diagnosis is via a combination of clinical findings, hormone levels, provocation tests, and brain imaging. Treatment is hormonal replacement and addressing the underlying etiology.
  • Pituitary adenoma: tumors that develop within the anterior lobe of the pituitary gland. Pituitary adenomas are classified by size (either microadenomas or macroadenomas) and their ability to secrete hormones. Nonfunctioning or nonsecretory adenomas do not secrete hormones but can compress surrounding pituitary tissue, leading to hypopituitarism. Secretory adenomas secrete various hormones depending on the cell type from which they evolve, leading to hyperpituitarism. 
  • Hyperprolactinemia: elevated levels of prolactin in the blood. The most common cause of hyperprolactinemia is a prolactin-secreting adenoma known as a prolactinoma. Presentations can include galactorrhea (milky discharge), oligomenorrhea, erectile dysfunction, and in the case of large tumors, headaches and visual changes. 
  • Acromegaly and gigantism: caused by excess production of pituitary GH. Typically, gigantism refers to the tall stature seen in excess GH states in children before growth plate closure, and acromegaly is the result of excess GH after growth plate closure leading to large extremities and characteristic facies. 
  • Secondary adrenal insufficiency: condition in which there is insufficient production of ACTH in the pituitary gland, resulting in atrophy of the adrenal glands and adrenal insufficiency. Secondary adrenal insufficiency presents clinically with signs of low glucocorticoids (fatigue, weight loss, hypotension, and hypoglycemia), low mineralocorticoids (hypotension, hyperkalemia, and hyponatremia), and low androgens (low libido, loss of sexual hair, and amenorrhea in women).
  • Central diabetes insipidus (DI): condition in which the kidneys are unable to concentrate urine because of a lack of circulating ADH. These low levels of ADH are due to either decreased production within the hypothalamus or decreased release from the posterior pituitary gland. Presentation is with polyuria, nocturia, and polydipsia. Central and nephrogenic DI are differentiated based on measured ADH levels and response to the water deprivation test. Central DI is treated with desmopressin.
  • Syndrome of inappropriate antidiuretic hormone (SIADH):  disorder of impaired water excretion due to the inability to suppress the secretion of ADH. This syndrome can be due to various causes, including increased production by the pituitary gland due to trauma, disease, or certain medications, the ectopic secretion of ADH by cancer, or hereditary causes (nephrogenic SIADH). Syndrome of inappropriate antidiuretic hormone should be suspected in any individual with hyponatremia, hypoosmolality, and high urine osmolality.

References

  1. Welt, C. K. (2021). Hypothalamic-pituitary axis. UpToDate. Retrieved August 13, 2021, from https://www.uptodate.com/contents/hypothalamic-pituitary-axis 
  2. Ganapathy, M.K. (2021). Anatomy, head and neck, pituitary gland. StatPearls. Retrieved August 13, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/692/ 
  3. M.D., A. K. L., & M.D., T. L. (2019). Histology and Cell Biology: An Introduction to Pathology, 5th ed. Elsevier.

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