Chapter 5 - Endocrine Physiology

Question 1

Hypothalamic-Pituitary-Adrenal Axis

Answer 1

Cortisol - blood pressure, blood sugar, stress

Hypothalamus releases a corticotrophin-releasing hormone (CRH), and this stimulates the release of adrenocorticotrophic hormone (ACTH) by the anterior pituitary to general circulation, ACTH stimulates the release of cortisol (a glucocorticoid) from the adrenal cortex which is essential for maintaining normal plasma glucose concentration and blood pressure, it is also a suppressor of the immune response and can be used to treat chronic inflammatory diseases
(CRH (peptide)–> ACTH (peptide) –> cortisol (steroid)–> maintain normal blood glucose and blood pressure)

Question 2

Hypothalamic-Pituitary-Adrenal Axis Negative Feedback

Answer 2

Cortisol suppresses ACTH production by anterior pituitary and CRH production by hypothalamus

Question 3

Adrenal Cortical Diseases

Answer 3

Adrenal Gland (primary adrenal insufficiency) - adrenal cortex can’t produce cortisol, so hypothalamus will increase CRH production and anterior pituitary will increase ACTH secretion in response to low cortisol concentration (high CRH, high ACTH, low cortisol)

Anterior Pituitary (Secondary adrenal insufficiency) - the anterior pituitary gland can’t produce ACTH so the adrenal cortex decreases cortisol secretion, this causes the hypothalamus to increase CRH secretion in response to low cortisol plasma levels (high CRH, low ACTH and low cortisol)

Hypothalamus (Tertiary adrenal insufficiency) - Hypothalamus is unable to secrete CRH, anterior pituitary decreases ACTH secretion and the adrenal cortex decreases cortisol secretion (all low)

Question 4

Addison’s Disease

Answer 4

A type of primary adrenal insufficiency - low plasma glucose concentration, high ACTH low blood pressure, low aldosterone, and fatigue

Treatment: surgery, oral glucocorticoid and mineralcorticoid

Question 5

Glucocorticoid drugs

Answer 5

Can cause inhibition of ACTH and cortisol secretion (stopping these drugs abruptly can cause secondary adrenal insufficiency), need to reduce dose gradually

Question 6

Cushing’s syndrome

Answer 6

caused by ACTH secreting tumors in anterior pituitary or cortisol-secreting tumors in adrenal gland leads to abnormally high plasma concentrations of cortisol and glucose, abnormal fat distribution to face and abdomen, and loss of muscle in thighs and legs, diabetic presentation, chronic infections, increased appetite, hypertension

Treatment: surgery

Question 7

Hypothalamic-Pituitary-Thyroid Axis (and negative feedback)

Answer 7

Thyroid hormone influences basal metabolism, sympathetic nervous system, fetal and postnatal growth and brain development

Hypothalamus secretes thyrotropin releasing hormone (TRH, peptide), stimulates anterior pituitary to secrete thyroid-stimulating hormones (TSH, peptide) into circulation which stimulates thyroid gland to secrete two thyroid hormones (T3 and T4, iodinated tyrosine dimers)

T3 and T4 inhibit the TRH secretion by hypothalamus and TSH secretion by anterior pituitary

(TRH–>TSH–>T3,T4 –> brain development and metabolism)

Question 8

Mechanism of thyroid hormones synthesis and Deficiency of Iodine

Answer 8

Follicular colloid cells sequester Iodine from the blood via an Na+/I- co-transporter and use it in the synthesis of T3 and T4

Iodine deficiency - low T3 and T4, negative feedback to hypothalamus leads to overproduction of TRH and RSH

Question 9

Grave’s Disease

Answer 9

Autoimmune disease of hyperthyroidism, autoimmune antibodies stimulate TSH receptors in thyroid gland causing excessive secretion of thyroid hormones into circulation and the enlargement of the gland as goiter in the neck, very high levels of thyroid concentration in the blood, abnormally low TSH in blood, high heart rate, high basal metabolic rate and weight loss

Question 10

Hashimoto’s Disease

Answer 10

Autoimmune disease of hypothyroidism, immune cells and autoimmune antibodies destroy thyroid follicles, abnormally low plasma concentrations of thyroid hormones, abnormally high blood concentrations of TSH and abnormally low metabolic rate

Symptoms: fatigue, cold, weight gain, hair loss, constipation, slow pulse

Question 11

Hypothalamic-Pituitary-Gonad Axis

Answer 11

Hypothalamus secretes gonadotropin-releasing hormone (GnRH) which stimulates the anterior pituitary gland to secrete two hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), FSH stimulates germ cell production and LH stimulates reproductive hormone secretion (these stimulate secondary sexual characteristics by regulating gene expression)

(GnRH–>FSH –> germ cell production, GnRH–>LH–> reproductive hormone secretion)

Question 12

Female and male endocrine system

Answer 12

Female - FSH stimulates egg development and LH stimulates the secretion of estrogen and progesterone
By negative feedback estrogen and progesterone inhibit GnRH secretion by the hypothalamus and LH secretion by the anterior pituitary

Male - FSH stimulates sperm development and LH stimulates secretion of testosterone by the testes

Question 13

Hypothalamic-Pituitary-Liver(IGF) Axis and Negative Feedback

Answer 13

Growth hormone is postnatal only, it causes secretion of IGF-1 by liver, bone lengthening and thickening, increase in lean mass (protein synthesis), anti-insulin by raising blood glucose levels, effects circadian rhythm, excessive secretion in well-fed adolescents can lead to gigantism, children having malnutrition (bc of starvation or inflammatory bowl disease) have retarded growth because liver is unable to secrete a normal level of IGF-1 and the blood concentration of growth hormone may be abnormally high in these children (restoration of nutrition usually leads to catch-up in these children)

**GH levels surge during exercise and enhance exercise performance (but GH administration has side effects)

Hypothalamus secretes two hormones, growth hormone releasing hormone (GHRH) and somatostatin, GHRH stimulates and somatostatin inhibits growth hormone secretion by the anterior pituitary, growth hormones then stimulates the liver to secrete insulin-like growth factor-1 (IGF-1) which is the major mediator of bone growth

IGF-1 inhibits GHRH secretion and stimulates somatostatin secretion by the hypothalamus and inhibits growth hormone secretion by anterior pituitary

After closing of growth plate in adults, excessive secretion of growth hormone and/or IGF-1 can lead to acromegaly (thickening of fingers and broadening of face)

(GHRH–>stimulates —> growth hormone secretion —> IGF-1–> bone growth)

(Somatostatin –> inhibits –> growth hormone secretion –> less IGF-1 –> less bone growth)

Question 14

Hypothalamic Regulation of Prolactin Secretion and Negative Feedback

Answer 14

Anterior pituitary can release prolactin (in non pregnant females this is usually very low because dopamine released by hypothalamic neurons inhibit prolactin secretion), TRH weakly stimulates prolactin secretion by the anterior pituitary

Prolactin stimulates the secretion of dopamine and inhibits TRH secretion (negative feedback), some anti-depressants that block dopaminergic receptor activity can cause increase in prolactin, breast enlargement, and milk production in non-pregnant females (hyperprolactinemia)

During late pregnancy, high plasma concentration of estrogen overcomes inhibition of dopamine (amine) on prolactin secretion and causes high concentration of prolactin (peptide) and breast enlargement, breastfeeding stimulates milk production via a reflect where suckling stimulates the anterior pituitary to secrete prolactin by inhibiting hypothalamic release of dopamine

(hypothalamus releases dopamine –> inhibits prolactin from anterior pituitary)

(TRH from hypothalamus –> prolactin –> breast enlargement and milk production)

Question 15

Posterior Pituitary Hormones

Answer 15

Oxytocin and antidiuretic hormone are synthesized by hypothalamic neurons then released via nerve ending in the posterior pituitary gland

Oxytocin is essential for stimulating uterine smooth muscle contraction during labor (pushes baby towards cervix) and milk ejection during breast feeding

Antidiuretic hormone regulates extracellular fluid osmolarity by regulating urinary excretion of water (aldosterone, vasopressin, ADH), osmoreceptors detect increase in osmolarity and stimulate release of ADH/VP from posterior pituitary causing increase in water resorption and urine osmolarity

Question 16

Parathyroid Hormone and Vitamin D

Answer 16

There are 4 parathyroid glands within the thyroid gland, parathyroid hormone is essential for maintaining plasma calcium concentration within physiological range

Parathyroid hormone (peptide) increases calcium concentration via 2 mechanisms: directly stimulates calcium release from bone resorption and calcium reabsorption in the kidney, indirectly increases plasma calcium concentration by enhancing activation of vitamin D by hydroxylation in the kidney (we get this exogenously from food or endogenously by skin cells in response to UV irradiation), this activation increases the intestinal absorption of calcium (deficiency can lead to bone demineralization and deformation, disease known as rickets), hyperparathyroidism can lead to excessive bone resorption and osteoporosis

Question 17

Gastrointestinal and Pancreatic Hormones

Answer 17

The gastrointestinal tract and pancreas contain endocrine cells, gastrointestinal hormones regulate gastrointestinal motility, secretion and appetite, pancreatic hormones regulate energy metabolism and plasma glucose concentration

Question 18

Renin-Angiotensin-Aldosterone System

Answer 18

For regulation of total extracellular Na+ - Liver releases angiotensinogen–> (stimulated by renin) angiotensin I –> angiotensin II –> sympathetic activity, H2O retention, aldosterone secretion by adrenal gland, vasoconstriction, increase in BP (water and salt retention, circulation volume increases, this inhibits kidney release of renin which stimulates this whole process)

Question 19

Protein Hormones

Answer 19

water-soluble, exist as free molecules in circulation, bind to receptors on cell membranes of target cells, activate GPCR cascade (example is growth hormones and insulin)

Question 20

Amine and Steroid Hormones

Answer 20

lipid soluble, bound to carrier proteins in circulation and usually bind to cytoplasmic or nuclear receptors in target cells and trigger changes in gene transcription (some also bind to receptors on cell membranes), example is amine hormone = thyroid hormones, steroids = cortisol (sugar/stress), testosterone and estrogen (sex), and mineralcorticoid (salt)

Question 21

Pituitary Gland Parts

Answer 21

has an anterior and posterior portion (in brain)

Question 22

Posterior Pituitary gland

Answer 22

Contains projections from endocrine cells in the hypothalamus, hormones are synthesized in the hypothalamus and released in the posterior pituitary gland

Question 23

Anterior Pituitary gland

Answer 23

Part of hypothalamic-pituitary-endocrine gland system, has a cascade of hypothalamic hormone(s) (HH) carried by capillary networks in the hypothalamus to capillary networks in the anterior pituitary (hypophyseal portal circulation), they then inhibit or stimulate release of anterior pituitary hormones(S) (PH), which then go into general circulation and cause release of target hormones (TH) released by a peripheral endocrine gland