Pituitary Gland – Comprehensive Study Notes

Pituitary Gland: Structure and Location

• Small gland located in a bony cavity (sella turcica) just below the hypothalamus
• Connects to the hypothalamus by a thin stalk (infundibulum / pituitary stalk)
• Two anatomically and functionally distinct lobes:
  • Posterior pituitary (neurohypophysis): composed of nervous tissue
  • Anterior pituitary (adenohypophysis): consists of glandular epithelial tissue
  • Intermediate pituitary (pars intermedia) is present in development and in some species; in humans it is largely regressed in adulthood

Hypothalamic Connections and Anatomy

• Pituitary sits in relation to the hypothalamus and other brain structures; connection via infundibulum
• Enlarged view shows the connection to the hypothalamus and its relation to rest of the brain
• Hypothalamic-pituitary axis components:
  • Hypothalamic nuclei: Paraventricular nucleus, Supraoptic nucleus, Arcuate nucleus, Mammillary bodies, etc.
  • Hypothalamic tracts: Supraopticohypophyseal tract, Tuberohypophyseal tract, Hypothalamohypophyseal tract
  • Infundibulum (pituitary stalk) connects hypothalamus to the pituitary
  • Pars tuberalis surrounds the infundibulum and links to the anterior lobe
  • Neurohypophysis (posterior lobe) and Adenohypophysis (anterior lobe) receive distinct regulatory inputs
• Key brain landmarks near pituitary: Optic chiasm, Lamina terminalis, Median eminence of tuber cinereum, Dorsomedial, Ventromedial, and Arcuate hypothalamic regions, Mammillary bodies

Neurohypophysis (Posterior Pituitary)

• Part of the posterior lobe; does not synthesize hormones itself
• Stores and releases two peptide hormones produced by hypothalamic magnocellular neurons:
  • Anti-diuretic hormone (ADH) / Vasopressin: conserves water during urine formation
  • Oxytocin: stimulates uterine contractions during childbirth and milk ejection during lactation
• Structural/functional pathway:
  • Magnocellular neurons in the Paraventricular (PVN) and Supraoptic (SON) nuclei synthesize prohormones, package into secretory granules, and transport down axons via the hypothalamo-hypophyseal tract
  • Prohormone processing occurs within secretory granules; secretory vesicles are stored in the posterior pituitary (pars nervosa)
  • Exocytosis near capillary beds releases hormone along with neurophysin
  • Release is triggered by neuronal activity, delivering hormones directly into hypophyseal veins surrounding the posterior lobe
• Referenced process steps (simplified):
  • Synthesis of prohormone → packaging with prohormone convertases → secretory granules
  • Intra-axonal transport → cleavage of prohormone → storage of secretory vesicles
  • Exocytosis near capillary bed → release of hormone and neurophysin

Hypothalamic-Neurohypophyseal System: Magnocellular Pathway

• Magnocellular neurons located in PVN and SON
• Key steps include: synthesis, packaging with neurophysin, axonal transport, storage, and release to regulate peripheral targets via the posterior pituitary

Anterior Pituitary (Adenohypophysis)

• Secretes six peptide hormones produced within the pituitary:
  • Tropic hormones:
  • Thyroid-stimulating hormone (TSH)
  • Adrenocorticotropic hormone (ACTH)
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Growth hormone (GH)
  • Not a tropic hormone:
  • Prolactin (PRL)
• The six hormones act on various target organs and tissues; regulation is via hypothalamic releasing/inhibiting hormones

Hypothalamic Releasing Hormones and Regulation of the Anterior Pituitary

• Hypothalamic hormones that regulate the anterior pituitary include:
  • TRH ( Thyrotropin-releasing hormone )
  • CRH ( Corticotropin-releasing hormone )
  • GnRH ( Gonadotropin-releasing hormone )
  • GHRH ( Growth hormone-releasing hormone )
  • Dopamine – inhibitory
• These releasing/inhibiting hormones control the secretion of the respective anterior pituitary hormones

Hypothalamic Regulation of Anterior Pituitary Hormones: Hormone Targets and Actions

• TSH (from anterior pituitary) acts on the thyroid gland to promote thyroid hormone production; thyroid hormone includes T3 and T4
• ACTH acts on the adrenal cortex to promote cortisol production; cortisol participates in metabolic actions and stress response
• GH acts on liver and other tissues to stimulate IGF-I production and growth of soft tissues, bone, and other targets; GH has direct and indirect (IGF-1 mediated) effects
• FSH and LH act on the gonads to regulate sex hormone secretion (estrogen, progesterone, testosterone) and gametogenesis (ova and sperm)
• PRL acts on mammary glands to promote milk production
• Hormones and their peripheral target organs (illustrative mappings):
  • TSH → Thyroid gland; thyroid hormone synthesis and release
  • ACTH → Adrenal cortex; cortisol production
  • GH → Liver (and other tissues) to produce IGF-1; growth and metabolic effects
  • FSH/LH → Gonads; sex hormone production and gametogenesis
  • PRL → Mammary glands; milk production
• Peripheral hormones and intermediary actions:
  • IGF-1 mediates many growth-promoting effects of GH
  • Sex steroids provide feedback to hypothalamus and anterior pituitary to regulate release
  • Thyroid hormones (T3/T4) and cortisol provide feedback to hypothalamus and pituitary
• Receptor and signaling notes:
  • PRL receptor (JAK/STAT–linked)
  • GH receptor (JAK/STAT–linked)
  • FSH/LH receptors (Gs-linked GPCRs)
  • TSH receptor (Gs-linked GPCR)
  • MC2R (ACTH receptor) (Gs-linked GPCR)
• Endocrine target status: some targets are endocrine glands; others are directly responsive tissues (e.g., IGF-1 production by liver influences growth)

Short vs. Long Feedback Loops

• Primary hypothalamic regulation involves releasing/inhibiting hormones (TRH, CRH, GnRH, GHRH) and dopamine
• Short feedback loops: peripheral hormones influence the pituitary and hypothalamus directly
• Long feedback loops: peripheral hormones (e.g., T3/T4, cortisol, estrogens/testosterone) provide negative feedback to hypothalamus and pituitary to modulate hormone release
• Key hormone–receptor interactions and examples of regulatory dynamics:
  • Prolactin has autoregulatory and receptor-mediated feedback mechanisms
  • GH and IGF-1 provide negative feedback at the level of the hypothalamus and pituitary
• Listed cell types and their regulating hormones (simplified):
  • Corticotrope: ACTH; regulated by CRH and cortisol; CRH stimulates, cortisol provides feedback
  • Thyrotrope: TSH; regulated by TRH and thyroid hormones
  • Gonadotrope: FSH and LH; regulated by GnRH and sex steroids
  • Somatotrope: GH; regulated by GHRH and somatostatin
  • Lactotrope: PRL; regulated by dopamine (inhibitory) and other stimuli
• Tropic hormones and target organs: a note that many receptors are located on endocrine glands and mediate endocrine cascades via signaling pathways

Pituitary Blood Flow and Portal System

• Blood supply and drainage pattern:
  • Superior hypophyseal arteries feed into the primary capillary plexus within the pituitary stalk/infundibulum
  • Long portal veins connect to the secondary capillary plexus in the anterior lobe (hypophyseal portal system)
  • Short portal veins connect the primary and secondary plexuses
  • The anterior lobe is supplied by the hypophyseal portal system; the posterior lobe is served by directly entering arteries (inferior hypophyseal arteries) and draining via hypophyseal veins
• Venous drainage:
  • Posterior lobe drains into hypophyseal veins → cavernous sinus → inferior petrosal sinus → jugular vein
• Structural components shown in the portal system diagram include:
  • Fibrous tissue, primary plexus, long portal veins, trabecular arteries, short portal veins, secondary plexus, inferior hypophyseal arteries/veins, and the connections to the cavernous sinus

Pituitary Development: Embryology and Key Signals

• Embryonic origins:
  • Rathke's pouch (oral ectoderm) forms the anterior pituitary (adenohypophysis)
  • Infundibulum (diencephalon floor) forms the posterior pituitary (neurohypophysis) along with the neurohypophyseal stalk
  • Median eminence and infundibular stem become part of the hypothalamic-pituitary axis
• Early developmental interactions:
  • Rathke's pouch grows toward the brain and induces development of adenohypophysis; stalk regresses as the pouch forms the anterior lobe
  • Infundibulum forms the posterior lobe and neurohypophysis
  • Pars tuberalis surrounds the infundibulum
  • Pars intermedia is present in development; in adults it may be regressed/undetectable
• Components and adult anatomy (from development):
  • Adenohypophysis includes Pars distalis and Pars tuberalis; Pars intermedia is lost or reduced
  • Neurohypophysis includes Pars nervosa; fluid-filled spaces can persist as remnants of Rathke's pouch lumen
• Key transcription factors and lineage specification (from developmental schematics):
  • GATA-2, Prop-1, NeuroD1, Tpit, LIF, Pit-1 drive lineage specification in Rathke’s pouch
  • Pit-1 drives differentiation of somatotropes, lactotropes, and certain gonadotropes
  • Gonadotropes, Thyrotropes, Lactotropes, Somatotropes, and Corticotropes arise from Rathke’s pouch lineage
  • Additional progenitor and patterning factors involved in Rathke’s pouch development include:
  • Six3/6, Lhx3, Hesx1, Sox2, Sox1/2/3, Notch1/2, Jagged1, Hes1
  • BMP2, BMP4, Wnt4, FGF8/10/18, SHH (not explicitly listed but commonly implicated in pituitary development), and Pax family members in broader contexts
• Rhythms of development and morphological events:
  • Rathke’s pouch proliferates from oral ectoderm and expands toward the diencephalon
  • The stalk of Rathke’s pouch regresses; mesenchymal interactions and bone formation (developing sphenoid bone) envelop the pituitary
  • Median eminence and infundibulum form the hypothalamic connection to the posterior pituitary
• Notable structural remnants and anatomy references:
  • Optic chiasma, pars tuberalis, pars distalis, pars intermedia (lost in adult), infundibular stem, infundibular process, pars nervosa, fluid-filled spaces from lumen remnants
• Model of developmental gene regulation (illustrative):
  • Lineage commitment and organogenesis are driven by a network of transcription factors and signaling molecules; proto-typical pathways include GATA2/Prop1/NeuroD1/Tpit/Pit-1 in adenohypophysis specification and Sox2/Notch/Jagged in progenitor maintenance and differentiation

Key Hormonal Relationships and Practical Implications

• The hypothalamic-pituitary axis integrates neural and endocrine signals to regulate metabolism, growth, reproduction, and stress responses
• Hormone release is tightly coupled to feedback from target organs (thyroid hormones, cortisol, sex steroids, IGF-1)
• Understanding pituitary development helps explain congenital deficiencies and syndromes related to pituitary hormone production
• The posterior pituitary’s storage-and-release mechanism illustrates a neuroendocrine interface where neural signals trigger endocrine outcomes

Quick Reference: Hormones and Targets (Summary)

• Anterior Pituitary Hormones
  • TSH → Thyroid gland; thyroid hormone production and metabolic effects
  • ACTH → Adrenal cortex; cortisol production
  • FSH/LH → Gonads; sex hormone production and gametogenesis
  • GH → Liver (and other tissues); IGF-1 production; growth and metabolic effects
  • PRL → Mammary glands; milk production
• Posterior Pituitary Hormones
  • ADH (vasopressin) → Kidneys; water reabsorption
  • Oxytocin → Uterus and mammary glands; contraction and milk ejection
• Releasing/Inhibiting Hormones
  • TRH, CRH, GnRH, GHRH → Stimulate respective pituitary hormones
  • Dopamine → Inhibits prolactin release
• Feedback Signals
  • Peripheral hormones (T3/T4, cortisol, estrogens/testosterone/progesterone, IGF-1) feed back to hypothalamus/pituitary to regulate release
• Notable Biochemical Details
  • Prolactin molecular weight: ca. 23 kDa
  • Growth hormone molecular weight: ca. 22 kDa
  • CRH: 41-aa peptide; GHRH: 44-aa peptide; PRL receptor and GH receptor signaling via JAK/STAT pathways
  • CRH, TRH, GnRH, GHRH are short peptide hormones with specific receptor signaling mechanisms
• Receptor/Signal Examples
  • FSH/LH receptors: Gs-linked GPCRs
  • TSH receptor: Gs-linked GPCR
  • ACTH receptor (MC2R): Gs-linked GPCR

End of Notes