ANTERIOR PITUITARY HORMONES AND FEEDBACK CONTROL

Triple-Level Control

1. Hypothalamic Regulation
   • Releasing and inhibiting hormones (via the hypophysial portal circulation) act on G-protein–linked receptors in the pituitary, altering gene transcription and hormone secretion.
2. Target Gland Feedback
   • Circulating hormones from target glands (e.g., cortisol, thyroid hormone) exert negative feedback on their respective pituitary trophic hormones.
3. Intrapituitary Regulation
   • Autocrine and paracrine cytokines/growth factors locally modulate pituitary cell development and function.

Hypothalamic Releasing/Inhibiting Hormones

• Releasing Hormones: GHRH, CRH, TRH, GnRH.
• Inhibitory Hormones: Somatostatin (inhibits GH) and Dopamine (inhibits prolactin).

Anterior Pituitary Hormones

1. Corticotropin (ACTH)
2. Growth Hormone (GH)
3. Thyrotropin (TSH)
4. Follicle-Stimulating Hormone (FSH)
5. Luteinizing Hormone (LH)
6. Prolactin

• All are secreted pulsatilely into the systemic circulation.

Hypothalamic–Pituitary–Target Gland Feedback Loops

• Negative Feedback: Target gland hormones inhibit further pituitary/hypothalamic secretion (most common).
• Positive Feedback: The target gland hormone or a surrogate may enhance pituitary/hypothalamic release (less common).
• Closed Loop vs. Open Loop:
  • Closed Loop: Involves only the trophic hormone and its target gland hormone.
  • Open Loop: Includes influence from the nervous system (emotional or external stimuli) that can adjust or override the standard feedback.

Other Factors in Feedback

• Inhibin: A glycoprotein from Sertoli (testes) or granulosa (ovary) cells provides negative feedback on FSH secretion.
• Endogenous Secretory Rhythms:
  • Circadian / Diurnal Rhythms: ~24-hour cycle.
    • E.g., GH and prolactin peak after sleep onset; cortisol peaks ~2–6 AM, lowest ~11 PM; testosterone highest in the morning.
  • Ultradian Rhythms: Occur more frequently than once a day.
  • Infradian Rhythms: Periods longer than a day (e.g., menstrual cycle).

Clinical Considerations

• Pulsatile Secretion: A single GH measurement may not reflect overall GH status; IGF-1 is a more stable index.
• Time-of-Day Reference Ranges: E.g., cortisol reference range differs between morning and afternoon blood draws.
• Loss of Normal Rhythms: E.g., high midnight cortisol supports the diagnosis of Cushing syndrome (disrupted circadian rhythm).

POSTERIOR PITUITARY GLAND

Anatomy and Embryology

• Neural Tissue: Formed by the distal axons of neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus.
• Hormones Stored: Vasopressin (ADH) and Oxytocin.
• Vasopressin & Oxytocin: Nonapeptides (6–amino acid ring with disulfide bridge + 3–amino acid tail).
• Blood Supply: Inferior hypophysial arteries, draining into the cavernous sinus → internal jugular vein.

Storage and Release

• Storage Capacity: Enough vasopressin to sustain basal release ~30 days and maximal release ~5 days.
• Axonal Transport: ~90% of SON neurons produce vasopressin; the PVN also makes other peptides (somatostatin, CRH, TRH, opioids).
• Secretion: An action potential from SON/PVN travels down the axon, causing Ca²⁺ influx and exocytosis of neurosecretory granules into fenestrated capillaries in the posterior pituitary.

Posterior Pituitary Bright Spot

• MRI Feature: T1-weighted hyperintensity reflecting vasopressin stored in neurosecretory granules.
• Absent in central diabetes insipidus.
• Ectopic Location: In some congenital cases, the bright spot is found along the stalk or at the hypothalamic base; can be associated with a hypoplastic anterior pituitary and variable anterior pituitary dysfunction.