Hypothalamus, Pituitary, and Growth Hormone Physiology

A comprehensive set of 120 question-and-answer flashcards covering hormone classes, hypothalamic–pituitary regulation, feedback loops, growth-hormone physiology, IGF-1 actions, and related disorders.

What are the three major classes of anterior pituitary hormones?

Glycoproteins (TSH, LH, FSH), POMC-derived peptides (ACTH), and the GH/prolactin family.

Define a preprohormone.

An inactive peptide that contains a signal sequence; it is cleaved in the ER to form a prohormone, which is later processed into the active hormone.

How are peptide or protein hormones stored and released?

They are stored in membrane-bound secretory vesicles and released by Ca²⁺-dependent exocytosis.

From what precursor are steroid hormones synthesized?

Cholesterol; they are made in the mitochondria and cytoplasm and diffuse out immediately rather than being stored.

What is the biochemical origin of amine hormones?

They are derived from the amino acid tyrosine; catecholamines are stored in vesicles whereas thyroid hormones are not stored long term.

Which hypothalamic hormone inhibits prolactin secretion?

Dopamine (prolactin-inhibiting factor).

Which hypothalamic hormone stimulates growth-hormone release?

Growth Hormone–Releasing Hormone (GHRH).

Name the hypothalamic hormone that inhibits GH secretion.

Somatostatin (Growth Hormone–Inhibiting Hormone, GHIH).

Which hypothalamic hormone stimulates ACTH release?

Corticotropin-Releasing Hormone (CRH).

Which hypothalamic hormone stimulates TSH release?

Thyrotropin-Releasing Hormone (TRH).

Which hypothalamic hormone stimulates LH and FSH release?

Gonadotropin-Releasing Hormone (GnRH).

List two key features of hypothalamic releasing-hormone action.

They are released in pulses and act through membrane receptors that activate second-messenger pathways (cAMP, Ca²⁺/PKC).

What is long-loop negative feedback?

An end-organ hormone feeds back to inhibit both the hypothalamus and the anterior pituitary.

What is short-loop negative feedback?

A pituitary hormone feeds back to inhibit its own hypothalamic releasing hormone.

What vascular link connects hypothalamus to anterior pituitary?

The hypothalamo-hypophyseal portal system.

Name the two posterior pituitary hormones.

Antidiuretic Hormone (ADH, vasopressin) and oxytocin.

Where are ADH and oxytocin synthesized?

In magnocellular neurons of the supraoptic and paraventricular nuclei of the hypothalamus.

How do steroid hormones exert their cellular effects?

They bind intracellular receptors that act as transcription factors to modify gene expression.

How do peptide hormones signal within target cells?

They bind plasma-membrane receptors coupled to second-messenger systems such as cAMP, IP₃/DAG, or tyrosine kinases.

Why are circadian rhythms important for endocrine secretion?

Many hormones (e.g., ACTH, cortisol) are released in a pulsatile, circadian fashion synchronized to the sleep–wake cycle.

Define neuroendocrine cells.

Neurons that release hormones directly into the bloodstream.

Which lobe of the pituitary is glandular in origin?

The anterior pituitary (adenohypophysis).

Which lobe of the pituitary is a neural extension of the brain?

The posterior pituitary (neurohypophysis).

Give two primary stimuli for ADH release.

Increased plasma osmolality and decreased blood volume/pressure.

List three major stimuli for oxytocin secretion.

Suckling, cervical or uterine distension, and certain emotional cues.

What is the primary action of ACTH?

Stimulates cortisol synthesis and secretion from the zona fasciculata of the adrenal cortex.

What does TSH do at the thyroid gland?

Stimulates iodide uptake, thyroglobulin synthesis, and secretion of T₃ and T₄.

List four major actions of growth hormone (GH).

Stimulates protein synthesis, lipolysis, hepatic IGF-1 production, and linear growth of bone and soft tissues.

What is the principal action of prolactin?

Stimulates milk production (lactogenesis) in mammary glands.

What are the primary roles of LH and FSH?

Regulate gametogenesis and sex-steroid production in the gonads.

Which second messenger mediates GHRH action on somatotrophs?

cAMP (via Gs protein activation).

Which second messenger pathway is activated by TRH?

IP₃ and DAG through phospholipase C activation (Gq pathway).

What receptor type is most common for peptide hormones?

G protein-coupled receptors (GPCRs).

Identify the two main targets of vasopressin and their receptors.

Kidney collecting duct via V₂ receptors and vascular smooth muscle via V₁ receptors.

Name the two hypothalamic nuclei most important for posterior-pituitary hormone synthesis.

Supraoptic nucleus and paraventricular nucleus.

Which feedback loop explains cortisol suppression of CRH and ACTH?

Long-loop negative feedback.

How is prolactin secretion primarily controlled?

By tonic inhibition from hypothalamic dopamine acting on D₂ receptors of lactotrophs.

What is kisspeptin’s endocrine role?

Stimulates GnRH release; critical for onset of puberty.

Define a tropic hormone.

A hormone that stimulates another endocrine gland to secrete its hormone (e.g., TSH, ACTH).

Define a trophic hormone.

A hormone that promotes growth and nourishment of its target tissue.

What is the endocrine consequence of transecting the pituitary stalk?

Loss of most anterior-pituitary secretions except prolactin, which rises because dopaminergic inhibition is lost.

Which two anterior-pituitary hormones are inhibited by somatostatin?

Growth hormone (GH) and thyroid-stimulating hormone (TSH).

Where within the hypothalamus is CRH primarily produced?

Paraventricular nucleus.

What structure forms the connection between hypothalamus and posterior pituitary?

The infundibulum (pituitary stalk).

Compare the half-life of protein versus steroid hormones.

Protein hormones have short half-lives; steroid hormones have longer half-lives because they are protein-bound in plasma.

What is neuroendocrine integration?

Coordination between nervous and endocrine systems, largely via hypothalamic control of pituitary function.

Which anterior-pituitary cells synthesize GH?

Somatotrophs.

Describe the biosynthesis of GH within somatotrophs.

GH mRNA is transcribed from five exons, translated on rough ER, processed in the Golgi, and packaged into secretory granules.

List four physiologic stimulators of GH secretion.

Deep sleep, exercise, GHRH, and hypoglycemia.

List three inhibitors of GH secretion.

Somatostatin, IGF-1, and hyperglycemia.

Describe the normal daily pattern of GH release.

Pulsatile, with the largest pulses occurring shortly after onset of deep (slow-wave) sleep; ~70 % of daily GH is secreted during sleep.

Which intracellular signaling pathway mediates GH receptor action?

JAK2-STAT tyrosine-kinase pathway.

State the somatomedin hypothesis.

GH promotes growth indirectly by stimulating hepatic and local production of IGF-1, which acts on target tissues.

Name five major target tissues for GH and IGF-1.

Liver, bone, cartilage, skeletal muscle, and adipose tissue.

What is GH’s primary action in the liver?

Induces synthesis and secretion of IGF-1.

What is IGF-1’s main effect on bone?

Promotes clonal expansion of chondrocytes and extracellular matrix production at the growth plate.

Which thyroid hormone is required for GH-induced differentiation of cartilage?

Triiodothyronine (T₃).

What is GH’s effect on adipose tissue?

Stimulates lipolysis, decreasing fat mass.

How does GH affect glucose metabolism?

It is diabetogenic: decreases peripheral glucose uptake and increases hepatic glucose production, raising blood glucose.

How does IGF-1 signal in its target cells?

Binds to a transmembrane tyrosine-kinase receptor leading to activation of MAPK and PI3K pathways.

How do GH pulses change with aging (somatopause)?

Pulse amplitude and duration decline, leading to reduced overall GH secretion.

List four possible causes of dwarfism related to the GH axis.

GH deficiency, GHRH deficiency, GH receptor mutation (Laron syndrome), or IGF-1 deficiency.

What is Laron syndrome?

A form of dwarfism caused by GH receptor defects; GH levels are normal or high but IGF-1 is low.

Differentiate gigantism and acromegaly.

Gigantism results from GH excess before epiphyseal closure (childhood), whereas acromegaly occurs after closure (adulthood).

Give three typical physical signs of acromegaly.

Enlarged hands and feet, prognathism (protruding jaw), and organomegaly.

How is acromegaly confirmed biochemically?

Persistently elevated serum IGF-1 and failure of GH suppression during an oral glucose tolerance test.

Name three treatment options for acromegaly.

Surgical adenoma removal, somatostatin analogs (e.g., octreotide), and dopamine agonists (e.g., cabergoline).

What is GH’s effect on skeletal muscle?

Increases protein synthesis and lean body mass.

How does GH affect the immune system?

Enhances immune cell function and survival.

Describe the effect of IGF-1 on cartilage.

Stimulates matrix synthesis and proliferation of chondrocytes.

What body composition changes accompany the age-related fall in GH?

Reduced muscle mass, thinner skin, lower bone mineral content, and increased adiposity.

Explain feedback control of GH by IGF-1.

IGF-1 exerts long-loop negative feedback on both hypothalamic GHRH neurons and pituitary somatotrophs to suppress GH release.

Define somatomedins.

Insulin-like growth factors (IGF-1 and IGF-2) that mediate many of GH’s growth-promoting effects.

Name four other hormones (besides GH/IGF-1) important for growth.

Insulin, thyroid hormone, cortisol (physiologic levels), and sex steroids (especially during puberty).

During which life stage is GH secretion highest?

Adolescence/puberty.

What is the effect of sleep deprivation on GH secretion?

It markedly reduces nocturnal GH pulses and can impair growth in children.

How does GH act on the kidney?

Promotes sodium and water retention.

How does acute versus chronic stress affect GH levels?

Acute stress may transiently increase GH; prolonged stress (elevated cortisol) eventually suppresses GH.

Which neurotransmitter enhances GH secretion?

Dopamine (via hypothalamic stimulation).

What dynamic test assesses GH reserve?

Insulin-induced hypoglycemia test, which should provoke a GH surge in healthy individuals.

How does GH affect bone mineral density?

Stimulates periosteal bone growth and increases bone mineral density over time.

Describe the structural relationship between GH, prolactin, and hCS.

They share sequence homology and belong to the same cytokine hormone family; GH is species-specific.

What happens to GH levels during prolonged starvation?

They increase to conserve protein and mobilize fat stores via lipolysis.

What is GH’s effect on whole-body nitrogen balance?

Promotes a positive nitrogen balance by stimulating protein synthesis and reducing proteolysis.

In veterinary medicine, what condition did Priscilla the German-shepherd dog exhibit?

Pituitary dwarfism due to GH deficiency.

What laboratory pattern characterizes a GH receptor defect?

Elevated or normal GH with low IGF-1 and absent growth response.

Which lab values point to acromegaly?

High IGF-1, elevated fasting GH, and failure of GH suppression with oral glucose.

How does IGF-1 exert long-loop feedback?

It inhibits GHRH release from the hypothalamus and GH release from somatotrophs.

List three sequelae of untreated childhood GH deficiency.

Short stature (dwarfism), delayed puberty, and reduced muscle development.

Identify characteristic skeletal changes in acromegaly.

Periosteal bone thickening, enlarged mandible (prognathism), frontal bossing, and thickened digits.

How does a glucose tolerance test differentiate normal from acromegalic GH secretion?

GH falls in healthy individuals but remains high or rises in acromegaly.

Approximately what proportion of daily GH secretion occurs during deep sleep?

About 70 %.

Which organ makes most circulating IGF-1?

The liver.

Distinguish hypertrophy from hyperplasia.

Hypertrophy is an increase in cell size; hyperplasia is an increase in cell number.

What hypothalamic change contributes to somatopause?

Reduced secretion of GHRH.

What pituitary defect can cause GH deficiency?

Loss or dysfunction of somatotrophs (e.g., pituitary tumor, infarction, or genetic defect).

Which intracellular pathway is primarily activated by GH binding to its receptor?

JAK2-STAT signaling cascade.

Outline somatostatin’s inhibition of GH release at the cellular level.

Somatostatin activates Gi proteins → lowers cAMP → hyperpolarizes the cell → reduces Ca²⁺ entry → suppresses exocytosis of GH granules.

GH shares structural similarity with which two hormones?

Prolactin (PRL) and human chorionic somatomammotropin (hCS).

What is the primary role of somatomedins such as IGF-1?

To mediate GH’s anabolic and growth-promoting actions on tissues.