Endocrine Physiology: Hypothalamus, Pituitary, Calcium Homeostasis, and GI Hormones

Flashcards covering key vocabulary, anatomical structures, hormones, pathways, and clinical syndromes across the endocrine hypothalamus, posterior pituitary, calcium homeostasis, and gastrointestinal hormone systems.

Hypothalamus

A neuroendocrine coordinating center of the brain that acts as a transducer to convert neuronal activity into hormonal secretions, regulating cardiovascular, respiratory, gastrointestinal, and reproductive functions.

Tanycytes

Large cuboidal epithelial cells lining the floor of the third ventricle that connect the hypothalamus to the cerebrospinal fluid (CSF).

Tuberoinfundibular Tract

A hypothalamic axonal tract originating from parvicellular neurons in the arcuate, ventromedial, and paraventricular nuclei that terminates near the primary capillary plexus of the median eminence to control the anterior pituitary.

Hypothalamohypophysial Tract

A neural tract arising from magnocellular neurons in the supraoptic and paraventricular nuclei whose axons traverse the infundibulum to terminate directly in the posterior pituitary.

Neurovascular Hypothesis

The concept formulated by GW Harris (1955) proposing that hypothalamic neurosecretory factors are released into the hypophyseal portal circulation to regulate anterior pituitary hormone secretion.

Long-Loop Feedback

A regulatory negative feedback loop wherein hormones secreted by ultimate peripheral target glands (e.g., thyroid hormones, gonadal steroids, cortisol) inhibit the hypothalamus, pituitary, or higher CNS centers.

Short-Loop Feedback

A negative feedback mechanism in which anterior pituitary hormones feed back directly to regulate and inhibit hypothalamic hormone secretion.

Autoinhibition

A negative feedback mechanism whereby a secreted pituitary hormone acts back directly upon the pituitary gland itself to inhibit its own further release.

Thyrotropin-Releasing Hormone (TRH)

A modified hypothalamic tripeptide hormone with the structure $\text{(pyro)Glu-His-Pro-NH}_2$ that stimulates anterior pituitary thyrotrophs to release thyroid-stimulating hormone (TSH) via a GPCR-PLC-$\text{Ca}^{2+}$ cascade.

Growth Hormone-Releasing Hormone (GHRH)

A hypothalamic peptide hormone expressed in the arcuate and ventromedial nuclei that stimulates somatotrophs to synthesize and secrete growth hormone (GH) via a GPCR-adenylyl cyclase-cAMP-PKA pathway.

Somatostatin (SST)

A 14-amino acid peptide cleaved from a 28-amino acid precursor that is synthesized in the paraventricular nucleus and inhibits the secretion of GH and TSH by somatotrophs and thyrotrophs via adenylyl cyclase inhibition.

Prolactin Inhibitory Factor (PIF)

Dopamine synthesized and secreted by parvicellular neurons of the arcuate nucleus into the hypophyseal portal system, which tonically inhibits prolactin release from lactotrophs.

Hyperprolactinemia

A clinical condition marked by abnormally elevated circulating prolactin levels (up to $250\times$ normal), frequently caused by lactotroph adenomas and treated therapeutically with dopamine receptor agonists like bromocriptine.

Gonadotropin-Releasing Hormone (GnRH)

A decapeptide hormone produced in the arcuate nucleus that is released in pulsatile bursts into the portal system to stimulate the release of LH and FSH from pituitary gonadotrophs.

Corticotropin-Releasing Hormone (CRH)

A 41-amino acid hypothalamic peptide synthesized in parvicellular neurons of the paraventricular nucleus that stimulates anterior pituitary synthesis and release of adrenocorticotropic hormone (ACTH) from POMC.

Kallman's Syndrome

An X-linked genetic disorder caused by mutations in the KAL1 gene resulting in failure of GnRH neurons to migrate, leading to hypogonadotropic hypogonadism, absent or delayed puberty, and infertility.

Neurohypophysis

The posterior lobe of the pituitary gland formed by a downward neuroectodermal projection of the diencephalon, consisting of unmyelinated axons of magnocellular neurons and supportive pituicytes.

Pituicytes

Specialized glial/neuroglial supporting cells within the neurohypophysis that provide structural support and nourishment to magnocellular axon terminals.

Oxytocin (OT)

A nonapeptide neurohormone with a disulfide bridge between positions 1 and 6, containing isoleucine at position 3 and leucine at position 8, which stimulates uterine contractions and mammary myoepithelial cell contractions.

Neurophysin I

The specific protein carrier (oxyphysin) cleaved alongside oxytocin from prepro-oxytocin within axonal transport vesicles.

Milk Let-Down

The neuroendocrine reflex process wherein suckling activates afferent mechanoreceptors, triggering hypothalamic oxytocin release to contract mammary alveolar and ductal myoepithelial cells, forcibly ejecting milk.

Arginine Vasopressin (AVP)

A 9-amino acid neurohypophyseal hormone with phenylalanine at position 3 and arginine at position 8 that mediates water conservation via renal $V_2$ receptors and vasoconstriction via vascular $V_1$ receptors.

Neurophysin II

The carrier protein (pressophysin) cleaved from prepro-AVP alongside arginine vasopressin and a glycopeptide within neurosecretory vesicles.

Organum Vasculosum of the Lamina Terminalis (OVLT)

An anterior hypothalamic circumventricular structure housing central osmoreceptors that sense small changes in plasma osmolality to regulate AVP secretion.

Baroreceptors

Stretch receptors located in the carotid sinus and aortic arch that tonically inhibit AVP release via norepinephrine when blood pressure is normal, permitting AVP release when arterial pressure falls.

Aquaporin-2 (AQP2)

A vasopressin-regulated water channel protein that is phosphorylated and translocated from intracellular vesicles to the apical plasma membrane of renal collecting duct principal cells.

Diabetes Insipidus

A disorder characterized by polydipsia and the excretion of large volumes of dilute urine, caused by either deficient hypothalamic AVP synthesis (central) or renal insensitivity to AVP (nephrogenic).

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

A condition of autonomous, non-physiologic AVP secretion typically caused by tumors, resulting in excessive renal water retention, high urine concentration, increased blood volume, and dilutional hyponatremia.

Hydroxyapatite

The primary inorganic crystal lattice of bone matrix composed of calcium phosphate and calcium hydroxide, having the molecular formula $\text{Ca}_{10}(\text{PO}_4)_6(\text{OH})_2$.

Calmodulin

A ubiquitous intracellular calcium-sensor protein containing four EF-hand domains that undergoes a conformational change upon binding $\text{Ca}^{2+}$ to activate downstream enzymes such as myosin light-chain kinase (MLCK).

Osteoblasts

Bone-building cells of mesenchymal origin that synthesize and secrete collagen fibers, osteocalcin, and other organic matrix components (osteoid), and express surface RANKL to direct osteoclast differentiation.

Osteocytes

Mature bone cells that originate from osteoblasts trapped within the mineralized bone matrix, responsible for sensing mechanical strain and maintaining bone architecture.

Osteoclasts

Large, multinucleated bone-resorbing cells derived from the fusion of hematopoietic monocyte/macrophage lineage precursors that dissolve bone mineral and matrix via acid and protease secretion.

Ruffled Border

The specialized, heavily folded plasma membrane domain formed by active osteoclasts at the bone surface through which vacuolar $\text{H}^+\text{-ATPases}$ and chloride channels secrete hydrochloric acid.

Sealing Zone

A dense ring of actin microfilaments and adhesion molecules that tightly seals the osteoclast plasma membrane against the bone matrix, isolating the sub-osteoclastic resorption pit.

Parathyroid Hormone (PTH)

An 84-amino acid peptide hormone secreted by parathyroid chief cells in response to low extracellular $\text{Ca}^{2+}$ that stimulates bone resorption, increases renal calcium reabsorption, and promotes renal phosphate excretion.

Calcium-Sensing Receptor (CaSR)

A G-protein-coupled receptor on parathyroid chief cells and thyroid C cells that senses extracellular ionized calcium, suppressing PTH secretion via $G_{\alpha i}$ and $G_{\alpha q}$ when bound to $\text{Ca}^{2+}$.

RANKL

Receptor Activator of Nuclear Factor $\kappa$B Ligand; a surface protein expressed on osteoblastic cells that binds RANK on osteoclast precursors to induce osteoclastogenesis.

Osteoprotegerin (OPG)

A soluble decoy receptor secreted by osteoblasts that binds and neutralizes RANKL, preventing it from activating RANK and thereby inhibiting osteoclast formation.

Parathyroid Hormone-Related Peptide (PTHrP)

A peptide homologous to PTH at its amino terminus that binds the PTH-1 receptor; produced by certain tumors to cause humoral hypercalcemia of malignancy.

Calcitonin

A 32-amino acid hypocalcemic peptide hormone containing an N-terminal disulfide loop, secreted by parafollicular C cells of the thyroid to inhibit osteoclastic bone resorption and increase urinary calcium excretion.

Parafollicular C Cells

Clear neuroendocrine cells dispersed between thyroid follicles that synthesize and secrete calcitonin in response to elevated blood $\text{Ca}^{2+}$ levels.

Calcitriol ($1,25\text{-(OH)}_2\text{-D}_3$)

The active metabolite of vitamin D, generated in the kidney by $1\alpha\text{-hydroxylase}$ under PTH stimulation, which increases intestinal calcium and phosphate absorption via calbindin induction.

Denosumab (Prolia)

A pharmaceutical monoclonal antibody that acts as an OPG mimic by binding RANKL, used in postmenopausal osteoporosis to inhibit osteoclastogenesis and prevent bone resorption.

Parietal Cells

Oxyntic epithelial cells of the gastric glands that synthesize and secrete hydrochloric acid (HCl) into the lumen via apical $\text{H}^+/\text{K}^+\text{-ATPase}$ pumps in response to gastrin, histamine, and acetylcholine.

Peptic Cells

Chief cells located in the base of gastric glands that synthesize and release pepsinogen, an inactive proenzyme that undergoes acid-catalyzed conversion to active pepsin.

Gastrin

A gastrointestinal peptide hormone produced by antral G cells (circulating mainly as gastrin-34 and gastrin-17) that stimulates gastric acid secretion from parietal cells and induces histamine release from ECL cells.

Enterochromaffin-Like Cells (ECL Cells)

Neuroendocrine cells in the gastric mucosa that secrete histamine in response to gastrin stimulation, which then acts via $H_2$ receptors on parietal cells to stimulate acid production.

Zollinger-Ellison Syndrome

A hypergastrinemic condition caused by autonomous gastrin-secreting neuroendocrine tumors (gastrinomas), resulting in severe hyperchlorhydria and intractable gastrointestinal ulceration.

Cholecystokinin (CCK)

A gastrointestinal peptide secreted by duodenal I cells sharing a conserved C-terminus with gastrin, which stimulates pancreatic acinar enzyme secretion and contracts the gallbladder to release bile salts.

Monitoring Peptide

A trypsin-sensitive luminal factor secreted into the small intestine that binds I cells to stimulate CCK release, creating a self-limiting loop as trypsin degrades the peptide once dietary protein is digested.

Secretin

A 27-amino acid peptide hormone secreted by duodenal S cells when luminal pH falls below 4.5, stimulating pancreatic duct cells to secrete bicarbonate-rich fluid to neutralize gastric acid.

Gastric Inhibitory Peptide (GIP)

An incretin hormone of the secretin peptide family secreted by duodenal K cells in response to luminal glucose, which enhances glucose-dependent insulin secretion from pancreatic beta cells.

Ghrelin

A 28-amino acid orexigenic peptide produced primarily by endocrine cells in the gastric fundus during fasting that crosses the blood-brain barrier to stimulate hunger via hypothalamic NPY/AgRP neurons.

Leptin

A 167-amino acid anorexigenic hormone produced by white adipose tissue in proportion to fat mass, which acts in the arcuate nucleus to activate POMC/CART neurons and inhibit NPY/AgRP neurons.

NPY/AgRP Neurons

Orexigenic neurons in the hypothalamic arcuate nucleus stimulated by ghrelin and inhibited by leptin that release neuropeptide Y and agouti-related protein (an MC3R/MC4R antagonist) to promote food intake.

POMC/CART Neurons

Anorexigenic neurons in the hypothalamic arcuate nucleus that are activated by leptin and insulin to produce $\alpha\text{-MSH}$, which binds melanocortin-4 receptors (MC4R) to suppress appetite.

$$\alpha\text{-Melanocyte-Stimulating Hormone (}\alpha\text{-MSH)}$$

A tridecapeptide derivative of POMC produced in the brain and skin that acts in the hypothalamus as an appetite-suppressing neuropeptide and in the skin to stimulate melanin pigmentation.