9.2 Anterior & Posterior Pituitary Hormones

Anterior & Posterior Pituitary Hormones

The pituitary gland (hypophysis) is a small, pea-sized organ measuring roughly 1 to 1.5 centimeters in diameter and weighing approximately 0.5 grams in adults. Despite its modest size, it exercises profound regulatory dominance over growth, fluid osmolarity, basal metabolic rate, and human reproduction. Historically designated the "master gland" of the endocrine system, contemporary endocrinology recognizes that the pituitary is itself masterfully orchestrated by upstream neurosecretory nuclei of the hypothalamus.

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Anatomical Organization & Dual Embryological Origins

The pituitary gland is situated within the cranial vault at the base of the brain, seated securely in the sella turcica ("Turkish saddle"), a deep, saddle-shaped bony depression in the superior surface of the sphenoid bone. Superiorly, it is sheltered by a reflection of dura mater called the diaphragma sellae, and it resides directly inferior to the optic chiasm (explaining why expanding pituitary tumors characteristically compress the crossing optic nerve fibers, producing bitemporal hemianopia—loss of peripheral vision in both eyes).

The pituitary is partitioned into two functionally, histologically, and embryologically distinct lobes:

1. Anterior Pituitary (Adenohypophysis): Accounts for approximately 75% of total gland weight. It develops embryologically from an upward evagination of oral ectoderm from the roof of the primitive stomodeum, known as Rathke's pouch. Histologically, it is true glandular epithelium composed of densely packed parenchymal cells surrounded by a rich network of fenestrated sinusoidal capillaries.
2. Posterior Pituitary (Neurohypophysis): Accounts for the remaining 25% of gland weight. It originates embryologically from a downward neuroectodermal growth of the diencephalon. Histologically, it consists of unmyelinated nerve fibers, specialized glial support cells called pituicytes, and neurosecretory axon terminals containing neurohormone storage bodies.

Pituitary Gland (Hypophysis)
├── Anterior Lobe (Adenohypophysis, Glandular)
│   ├── Tropic Hormones: TSH, ACTH, FSH, LH (Regulate downstream glands)
│   └── Direct Effectors: GH (Growth Hormone), PRL (Prolactin)
└── Posterior Lobe (Neurohypophysis, Neural)
    ├── Stores & Releases: Antidiuretic Hormone (ADH / Vasopressin)
    └── Stores & Releases: Oxytocin

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Anterior Pituitary Hormones (Adenohypophysis)

The adenohypophysis synthesizes and secretes six major peptide and protein hormones. A standard clinical mnemonic to remember these hormones is FLAT PEG (the E, beta-endorphin, is cleaved from the same POMC precursor as ACTH and is not counted among the six major hormones):

• F: Follicle-Stimulating Hormone (FSH)
• L: Luteinizing Hormone (LH)
• A: Adrenocorticotropic Hormone (ACTH)
• T: Thyroid-Stimulating Hormone (TSH)
• P: Prolactin (PRL)
• E: Endorphins (endogenous analgesics)
• G: Growth Hormone (GH)

These hormones are divided into two functional classes:

• Tropic Hormones (FLAT): Regulate the endocrine secretory activity of another peripheral endocrine gland.
• Direct Effector Hormones (PEG): Act directly on non-endocrine somatic target tissues to produce metabolic or physiological responses.

1. Thyroid-Stimulating Hormone (TSH / Thyrotropin)

• Regulatory Control: Stimulated by hypothalamic thyrotropin-releasing hormone (TRH); inhibited by rising levels of circulating thyroid hormones ($T_3, T_4$) via negative feedback, as well as by somatostatin (GHIH).
• Target Tissue: Follicular cells of the thyroid gland.
• Physiological Action: Stimulates the active uptake of dietary iodide, synthesis of thyroglobulin, iodination of tyrosine, and the release of thyroxine ($T_4$) and triiodothyronine ($T_3$) into the bloodstream.

2. Adrenocorticotropic Hormone (ACTH / Corticotropin)

• Regulatory Control: Stimulated by hypothalamic corticotropin-releasing hormone (CRH). Secretion follows a marked diurnal circadian rhythm (surging in the early morning prior to waking) and spikes sharply in response to physiological and psychological stressors, systemic inflammation, and hypoglycemia. Suppressed by rising blood cortisol concentrations via negative feedback.
• Target Tissue: The adrenal cortex, specifically the middle steroidogenic layer, the zona fasciculata.
• Physiological Action: Stimulates the enzymatic cleavage of cholesterol into pregnenolone, driving the biosynthesis and secretion of glucocorticoids (predominantly cortisol), which mobilize fuel stores, suppress inflammatory cascades, and assist vascular tone maintenance.

3. Follicle-Stimulating Hormone (FSH, Gonadotropin)

• Regulatory Control: Stimulated by pulsatile pulses of hypothalamic gonadotropin-releasing hormone (GnRH). Suppressed by gonadal sex steroids and the peptide hormone inhibin.
• Target Tissues & Physiological Actions:
  • In Females: Binds to granulosa cells of ovarian follicles, stimulating follicular recruitment, granulosa cell proliferation, and estrogen secretion during the follicular phase of the ovarian cycle.
  • In Males: Binds to Sertoli (sustentacular) cells lining the seminiferous tubules of the testes, stimulating the synthesis of androgen-binding protein (ABP) and promoting healthy spermatogenesis.

4. Luteinizing Hormone (LH, Gonadotropin)

• Regulatory Control: Stimulated by pulsatile hypothalamic GnRH. High sustained levels of estrogen in late follicular phase trigger a positive feedback neuroendocrine surge of LH.
• Target Tissues & Physiological Actions:
  • In Females: The massive mid-cycle LH surge triggers the rupture of the mature preovulatory (Graafian) follicle, causing ovulation. Following ovulation, LH transforms the collapsed follicular wall into the corpus luteum and maintains its secretion of progesterone and estrogens during the luteal phase.
  • In Males: Binds to interstitial cells of Leydig situated between the seminiferous tubules in the testes, stimulating steroidogenesis and the secretion of testosterone.

5. Prolactin (PRL)

• Regulatory Control: Unique among anterior pituitary hormones because its secretion is under continuous, dominant tonic inhibition by hypothalamic dopamine (historically termed Prolactin-Inhibiting Hormone / PIH). TRH, suckling, and high circulating estrogens diminish dopamine release and promote prolactin secretion.
• Target Tissue: Alveolar glandular epithelium of the mammary glands.
• Physiological Action: Stimulates breast tissue development during pregnancy and promotes post-partum milk production (lactogenesis).
• High-Yield Clinical Distinction: Prolactin stimulates milk synthesis and production, whereas oxytocin stimulates milk ejection ("letdown") through myoepithelial contraction.

6. Growth Hormone (GH / Somatotropin)

• Regulatory Control: Stimulated by hypothalamic Growth Hormone-Releasing Hormone (GHRH) in nocturnal pulses (especially during stage 3/4 slow-wave sleep) and during exercise, fasting, or hypoglycemia. Inhibited by hypothalamic Growth Hormone-Inhibiting Hormone (GHIH / Somatostatin), elevated circulating free fatty acids, and high concentrations of GH and IGF-1 via negative feedback.
• Dual Mechanisms of Action:
  • Indirect Somatic Growth Actions: GH binds to cell-surface receptors on hepatocytes in the liver and peripheral tissues, stimulating the transcription and secretion of Insulin-like Growth Factors (IGFs, primarily IGF-1 / somatomedin C). IGF-1 stimulates chondrocyte mitosis and matrix deposition at the epiphyseal plates of long bones, promoting linear skeletal growth. In skeletal muscle, IGF-1 accelerates amino acid transport across sarcolemmal membranes and promotes ribosomal protein synthesis, increasing lean muscle mass.
  • Direct Metabolic Actions (Anti-Insulin / Diabetogenic Effect): GH acts directly on adipocytes to stimulate lipolysis (breakdown of triglycerides into free fatty acids and glycerol), mobilizing lipid fuels for cellular energy. Concurrently, GH inhibits cellular uptake and oxidation of glucose in skeletal muscle and adipose tissue while promoting hepatic gluconeogenesis. By conserving glucose and elevating blood glucose concentrations, GH produces an "anti-insulin" or diabetogenic effect.

Pathophysiology of Growth Hormone Secretion

• Pituitary Gigantism: Caused by chronic GH hypersecretion (typically an adenoma of somatotroph cells) beginning in childhood, prior to the closure of epiphyseal growth plates. The open cartilaginous growth plates respond to excessive IGF-1 with massive longitudinal bone extension, producing heights that can exceed 7 feet with relatively proportionate body dimensions.
• Acromegaly: Caused by chronic GH hypersecretion in adulthood, after the epiphyseal growth plates have ossified and closed. Longitudinal bone lengthening is impossible; instead, the excess GH and IGF-1 stimulate periosteal appositional bone growth and soft tissue hypertrophy. Manifestations include progressive broadening and widening of the hands, feet, and skull; protrusion of the mandible (prognathism); coarsening of facial features (frontal bossing, broadened nose); tongue enlargement (macroglossia); deepening of the voice; cardiomegaly; and severe peripheral insulin resistance.
• Pituitary Dwarfism (Growth Hormone Deficiency): Results from severe GH hyposecretion during childhood. Causes profound growth retardation and short stature (height below the third percentile), but body proportions remain completely symmetrical and cognitive development is unaffected (distinguishing it from the disproportionate limbs and cognitive impairment of congenital hypothyroidism).

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Posterior Pituitary Hormones (Neurohypophysis)

A critical, fundamental concept in endocrine physiology: The posterior pituitary does not synthesize hormones. It is a neurohemal storage and release organ consisting of approximately 100,000 unmyelinated axons whose cell bodies reside in the hypothalamus.

Posterior Pituitary Hormone Pathway

  Hypothalamic Nuclei (Supraoptic & Paraventricular)
  [Synthesize ADH and Oxytocin in Cell Bodies]
                    │
                    │ Axoplasmic Transport along
                    ▼ Hypothalamic-Hypophyseal Tract
  Posterior Pituitary (Neurohypophysis)
  [Stores Neurohormones in Axon Terminals / Herring Bodies]
                    │
                    │ Action Potential Evoked Exocytosis
                    ▼
  Inferior Hypophyseal Capillaries ───> Systemic Circulation

1. Antidiuretic Hormone (ADH / Vasopressin)

• Site of Synthesis: Synthesized predominantly by large neurosecretory cell bodies within the supraoptic nuclei of the hypothalamus, packaged into neurophysin carrier complexes, and transported down the hypothalamic-hypophyseal tract into the posterior lobe.
• Stimuli for Release:
  1. Hyperosmolarity: Central hypothalamic osmoreceptors detect even a subtle 1% to 2% increase in blood plasma osmolarity (such as during dehydration or high salt intake) and fire action potentials triggering immediate ADH release.
  2. Hypovolemia and Hypotension: Arterial and cardiopulmonary baroreceptors detect a substantial (10% to 15%) loss of blood volume or mean arterial pressure, stimulating massive ADH exocytosis.
• Mechanism of Action:
  • Renal Collecting Duct Water Conservation: ADH binds to basolateral membrane $V_2$ receptors (G-protein coupled receptors) on principal cells of the late distal convoluted tubules and renal collecting ducts. Activation of adenylate cyclase and protein kinase A causes intracellular storage endosomes containing Aquaporin-2 water channels to fuse with the apical (luminal) cell membrane. Water molecules rapidly diffuse down the steep osmotic gradient from the tubular urine filtrate into the hypertonic renal medullary interstitium, returning water to peritubular capillaries. The physiological result is a sharp reduction in urine volume, elevated urine specific gravity and osmolarity, and restoration of normal blood plasma osmolarity.
  • Vascular Arteriolar Constriction: At high physiological or pharmacological concentrations, ADH binds to vascular smooth muscle $V_1$ receptors linked to phospholipase C and intracellular calcium release, triggering systemic arteriolar vasoconstriction to elevate peripheral vascular resistance and restore arterial blood pressure (earning its alternative clinical name, vasopressin).
• Regulatory Inhibitors: Ethanol (alcohol) directly inhibits ADH secretion from the neurohypophysis, leading to renal water loss, copious dilute diuresis, and subsequent dehydration. (Caffeine's mild diuretic effect acts mainly within the kidney.)
• Clinical Pathologies of ADH:
  • Diabetes Insipidus (DI): Characterized by profound polyuria (excreting 5 to 20 liters of extremely dilute urine daily; specific gravity < 1.005) and severe compensatory polydipsia (unquenchable thirst). It arises from deficient hypothalamic synthesis or pituitary release of ADH (Central / Neurogenic DI, often following head trauma or neurosurgery) or renal collecting duct insensitivity to ADH (Nephrogenic DI). Essential Nursing Distinction: Unlike diabetes mellitus, the urine in diabetes insipidus contains no glucose (absence of glycosuria).
  • Syndrome of Inappropriate ADH (SIADH): Characterized by excessive, uninhibited ADH secretion (often due to small cell lung carcinoma, head injury, or stroke), resulting in severe fluid retention, extracellular volume expansion, dilutional hyponatremia (low serum sodium), muscle weakness, and cerebral edema.

2. Oxytocin

• Site of Synthesis: Synthesized predominantly by neurosecretory cell bodies within the paraventricular nuclei of the hypothalamus.
• Stimuli & Physiological Mechanisms:
  • Parturition (Labor and Delivery): As full-term labor begins, the fetal head pushes against and stretches the uterine cervix. Mechanical stretch receptors in the cervix generate afferent neural impulses that ascend the spinal cord to the hypothalamus, stimulating neurohypophyseal oxytocin release. Oxytocin binds to G-protein coupled receptors on uterine myometrial smooth muscle cells, increasing intracellular calcium flux and triggering forceful, rhythmic contractions. Contractions force the fetus further into the cervix, causing additional stretch, which fires more impulses, releasing even more oxytocin. This self-amplifying positive feedback loop (Ferguson reflex) continues with escalating intensity until delivery of the infant and placenta eliminates cervical stretch, breaking the loop.
  • Milk Ejection Reflex ("Letdown"): Tactile stimulation of the maternal nipple during infant suckling sends sensory neural signals through spinal pathways to the hypothalamus, triggering pulsatile oxytocin exocytosis. Oxytocin travels through the maternal bloodstream to the mammary glands, where it binds to myoepithelial cells surrounding the secretory alveoli. Myoepithelial contraction forces stored milk out of the alveoli into the lactiferous ducts and sinuses, ejecting milk into the nursing infant's mouth within 30 to 60 seconds of suckling onset.
  • Emotional and Social Attachment: Oxytocin functions as a central neurotransmitter facilitating maternal-infant bonding, interpersonal trust, empathy, and pair bonding.

Master Pituitary Hormones Reference Table