hormones

GRHR (growth hormone releasing hormone)

synthesis: neuropeptide synthesized by hypothalamic neurons and then secreted into the hypophyseal portal blood

regulation: secretion is inhibited by IGFs and SST

receptor: stimulatory GPCR on somatotroph cells

actions: stimulates GH (somatotropin) secretion by the anterior pituitary

somatostatin (SST)

synthesis: neuropeptide synthesized by the hypothalamus and secreted into the hypophyseal portal blood. also synthesized and released by pancreatic D cells

regulation: secretion is stimulated by GH and increased plasma glucose and arginine. secretion is inhibited by epinephrine and norepinephrine

receptor: inhibitory GPCR on somatotroph

actions: inhibits GH secretion by somatotroph cells. also inhibits the release of many other growth-promoting (trophic) hormones

growth hormone (GH)

synthesis: peptide hormone produced in somatotroph anterior pituitary cells

regulation: secretion is stimulated by GH releasing hormone (GHRH) and ghrelin. secretion is inhibited by somatostatin (SST) and IGF-1

actions: acts directly on target tissues and acts indirectly by increasing IGF-1 release

growth effects: induces growth (anabolic action) in almost every tissue

metabolic effects: stimulates “anabolic protein state” of cells, including increased amino acid uptake and protein synthesis. stimulates hyperglycemic state by inhibiting insulin action on glucose uptake in muscle, and by stimulating lipolysis in adipose tissue and gluconeogenesis in liver

circulates bound to plasma carrier proteins

IGF-1

insulin-like growth factor 1 (somatomedins)

regulation: secretion is stimulated by GH

actions: mediates most of the growth-promoting actions of GH. in childhood, GH and IGF-1 promote linear growth. in adulthood, GH and IGF-1 regulate body composition and may promote anabolic actions in muscle. circulates in plasma bound to high-affinity carrier proteins

leptin

synthesis: peptide made almost exclusively in adipocytes

regulation: secretion is tonic in proportion to adipose tissue mass

actions: crosses the blood-brain barrier and stimulates hypothalamic neurons that suppress appetite. important in intermediate to long-term regulation of appetite

ghrelin

synthesis: secreted by enteroendocrine cells

regulation: secretion is stimulated by fasting

actions: orexigenic (stimulates appetite) and stimulates GH secretion after a meal. therefore, contributes to body mass regulation and linear growth

cortisol

primary glucocorticoid hormone in humans

synthesis: cortisol is a steroid hormone derived from cholesterol by the adrenal cortex

regulation: cortisol secretion is stimulated by ACTH and AVP

receptor: cortisol binds to the glucocorticoid receptor (GR) in the cytoplasm. upon binding with cortisol, GR translocates to the nucleus to modulate gene transcription

target tissues: the glucocorticoid receptor is present in almost all cells

actions: cortisol’s main effect is raising plasma glucose levels. its actions on carbohydrate metabolism are similar to thyroid hormones: cortisol increases gluconeogenesis in liver, stimulates proteolysis in muscle (increasing plasma amino acids to be used for gluconeogenesis), and stimulates lipolysis (increasing plasma fatty acids and glycerol to be used for gluconeogenesis). cortisol also stimulates appetite, has immunosuppressive and anti-inflammitory activity

aldosterone

primary regulator of salt balance and ECF volume

synthesis: aldosterone is a steroid mineralocorticoid hormone derived from cholesterol (via progesterone) in the adrenal cortex. chemically, aldosterone is very similar to cortisol

regulation: aldosterone secretion is primarily stimulated by ANG II and high extracellular potassium concentration, with only a small effect of ACTH. secretion is inhibited by low extracellular potassium secretion

receptor: upon binding with cortisol, the receptors translocate to the nucleus, where they modulate gene transcription

actions: aldosterone stimulates Na reabsorption and K secretion by the renal tubule. in the renal tubule, aldosterone increases transcription of the Na-K pump (on the basolateral membrane), apical Na channels (ENaCs), and Na/K/Cl cotransporters

insulin

synthesis and breakdown: peptide secreted by pancreatic beta cells. rapidly degraded by enzymes

regulation: secretion is stimulated by hyperglycemia, but also by digestion (via vagus nerve activity and gastric hormone secretion). secretion is inhibited by epinephrine, norepinephrine, and somatostatin

receptor: tyrosine kinase associated receptor

actions: regulates glucose storage in target tissues, thereby maintaining plasma glucose concentration within narrow limits, which is essential for CNS function. during feeding, increased insulin secretion stimulates uptake of carbs, lipids, and amino acids by skeletal muscle, liver, and adipose tissue, replenishing their fuel reserves, which reduces plasma glucose concentration. during fasting, plasma insulin is low. this allows mobilization of lipids (from adipose tissue) for hepatic ketogenesis, and amino acids (especially from muscle) for hepatic gluconeogensis, which increases plasma glucose concentration.

glucagon

synthesis and breakdown: peptide secreted by pancreatic alpha cells. rapidly degraded

secretion: secretion is stimulated by ingestion of proteins (amino acids directly stimulate glucagon secretion by alpha cells). secretion is inhibited by plasma glucose (thus hypoglycemia increases secretion) and by somatostatin. secretion is stimulated by sympathetic nervous system.

receptor: stimulatory GPCR

target tissues: acts primarily on liver, but also acts on skeletal and cardiac muscle and adipose tissue

actions: effects of glucagon are mainly antagonistic to insulin. although glucagon release is stimulated primarily by amino acids, the primary action is regulation of carbohydrate and lipid metabolism. glucagon increases glycogenolysis, gluconeogenesis, ketogenesis, and lipolysis

parathyroid hormone (PTH)

functions primarily to increase plasma free calcium

synthesis: peptide hormone secreted by the parathyroid glands. rapidly degraded

secretion: synthesis and secretion is stimulated by hypocalcemia (low plasma free calcium)

receptor: stimulatory GPCR

target tissue: bone (osteoblasts), kidneys, and GI tract

actions: stimulates osteoclast activity, which dissolves bone, which, releases calcium and phosphate. increases calcium reabsorption and decreases phosphate reabsorption in the distal tubule and increases calcitriol synthesis. increases calcium absorption (via increased calcitriol in the GI tract)

calcitriol

calcitriol (vitamin D) functions primarily to promote bone mineralization

synthesis: PTH stimulates the formation of active vitamin D from vitamin D2 or vitamin D3

receptor: nuclear DNA transcription factor that regulates transcription of specific genes

target tissues: small intestine, kidneys, and bone

actions: calcitriol raises plasma calcium concentration and thus promotes bone mineralization

calcitonin

functions primarily to reduce plasma free calcium

synthesis: peptide hormone synthesized and secreted by parafollicular cells (c cells) of the thyroid gland

secretion: secretion is stimulated by hypercalcemia (c cells have calcium sensors). secretion is inhibited by hypocalcemia

receptor: stimulatory GPCR

target tissues: osteoclasts

actions: inhibit osteoclast activity, thereby increasing bone calcium deposition

anterior pituitary hormones

ACTH, GH, TSH, FSH, LH, Prolactin

TRH

target cell in anterior pituitary (AP): thyrotroph

hormone released by AP: TSH (thyrotropin)

target of AP hormone: thyroid cells, to make thyroid hormone

CRH

target cell in AP: corticotroph

hormone released by AP: ACTH (corticotropin)

target of AP hormone: adrenal cortex, to make corticosteroids

GnRH

target cell in AP: gonadotroph

hormone released by AP: FSH, LH (gonadotropins)

target of AP Hormone: ovarian cells, to make estrogens and progestins, initiate follicular growth and ovulation. testicular cells, to make testosterone, initiate spermatogenesis

inhibited by dopamine

target cell in AP: lactotroph

hormone released by AP: PRL

target of AP hormone: mammary glands, to initiate and maintain milk production

AVP

target of hypothalamic hormone: collecting duct, to increase water permeability

OT (oxytocin)

target of hypothalamic hormone: uterus and breast, to increase uterine contractions and milk letdown; may also promote social behavior and social bonding

peptide hormones

bind to cell-surface receptors and activate a variety of signal-transduction systems (GPCR and tyrosine kinase receptors). typically exist free in the circulation

amine hormones

• four classical amine hormones: epinephrine, norepinephrine, dopamine, and serotonin. however, amine hormones also include the thyroid hormones (T3 and T4), which act more like steroid hormones in terms of signal transduction and are therefore sometimes classified with lipid-derived hormones

• derived from tyrosine and tryptophan

• bind. tocell-surface GPCRs (except thyroid hormones)

• typically exist free in the circulation (except thyroid hormones)

steroid hormones

• derived from cholesterol and are hydrophobic/lipophilic

• enter target cells and bind to cytosolic and nuclear receptors that regulate gene transcription (slow-acting response). however, rapid responses are also known, so additional cytosolic receptor pathways must also exist

• cannot be stored in secretory vesicles so they are secreted as they are synthesized

• produced by only two tissues: adrenal cortex (mineralocorticoids, glucocorticoids, and small amounts of sex hormones) and gonads

thyroid hormones

• derived from iodination of tyrosine residues

• lipid soluble and are thus sometimes grouped with lipid derived hormones

• enter target cells and bind to cytosolic and nuclear receptors (thyroid hormone response elements) that regulate gene transcription (slow-acting response). however, as with steroid hormones, rapid responses to thyroid hormones are known, so additional cytosolic receptor pathways must also exist

• two hormones: T4 (less active form) and T3 (more active form)

• some T4 and T3 are transported in blood bound to carrier proteins

hypothalamic peptide hormones

AVP, CRH, GnRH, GHRH, Oxytocin, SST, TRH

tropic peptide hormones

ACTH, FSH, GH, LH, PRL, TSH

other peptide hormones

calcitonin, glucagon, insulin, IGFs, inhibin, PTH

amine hormones

dopamine, epinephrine, norepinephrine, serotonin, T3, T4

steroid hormones

aldosterone, cortisol, estradiol, progesterone, testosterone

enteric hormones

CCK, secretin, VIP