Hormone and Hormone Action

What are the two major internal communication and regulation systems in humans?

The nervous system and the endocrine system.

What is the origin and meaning of the word “hormone”?

It comes from the Greek word “hormaein,” meaning “to excite” or “to arouse.”

What is a hormone?

A chemical messenger secreted in very small amounts by specialized endocrine cells or ductless glands into the blood; it carries information to target cells and helps maintain homeostasis.

Why does a hormone affect some cells but not others?

Only target cells possessing the specific receptor for that hormone can respond to it.

What types of changes can hormones produce in target tissues?

Both short-term and long-term changes in the activity of glands, organs, and tissues.

What major processes do hormones coordinate at the whole-body level?

Ionic and fluid balance, energy metabolism, responses to the environment, growth and development, and reproduction.

What molecular processes can be regulated by hormones?

Gene transcription, protein synthesis and degradation, enzyme activity, protein conformation, and protein-protein interactions.

What cellular processes can be regulated by hormones?

Cell division, differentiation, death, motility, secretion, and nutrient uptake.

How are hormones broadly classified according to where their receptors act?

Hormones acting through cell-surface receptors and hormones entering cells to bind intracellular receptors.

How do most amino acid-based hormones produce their effects?

They bind cell-surface receptors and signal through second messengers or protein-protein interactions.

Why are thyroid hormones an exception among amino acid-derived hormones?

Although derived from amino acids, they are lipid-soluble, cross the plasma membrane, and bind intracellular receptors.

What are the main characteristics of steroid hormones?

They are synthesized from cholesterol, are lipid-soluble, cross the plasma membrane, and regulate transcription through intracellular receptors.

How do peptide hormones and steroid hormones differ in storage?

Peptide hormones are stored in secretory vesicles, whereas steroid hormones are synthesized enzymatically from cholesterol when needed and generally are not stored.

How are steroid and thyroid hormones transported through blood?

They circulate bound to plasma carrier proteins such as globulins and albumin.

What is the usual fate of most hormones after secretion?

They are rapidly degraded or inactivated; many have blood half-lives of less than 10 minutes.

What properties allow a receptor to respond selectively to a hormone?

It distinguishes its hormone from similar molecules, binds it at very low concentrations, changes conformation after binding, and initiates biochemical signaling.

At approximately what concentrations can hormone receptors bind their ligands?

Approximately 10^-8 to 10^-12 molar.

Why is a hormone called the first messenger?

It carries the extracellular signal to its receptor, which then generates or activates intracellular signaling molecules called second messengers.

What second messengers are emphasized in the slides?

Cyclic adenosine monophosphate (cAMP), calcium ions, diacylglycerol (DAG), and inositol 1,4,5-trisphosphate (IP3).

What are the three major classes of cell-surface receptors described?

G protein-coupled receptors, enzyme-linked receptors such as receptor tyrosine kinases, and ligand-gated ion channels.

What is the characteristic membrane structure of a G protein-coupled receptor?

A single polypeptide chain containing seven membrane-spanning alpha helices, each approximately 20-25 amino acids long.

What is the subunit composition of a heterotrimeric G protein?

One alpha subunit, one beta subunit, and one gamma subunit.

How do Gαs and Gαi have opposite effects on cAMP signaling?

Gαs activates adenylyl cyclase and raises cAMP, whereas Gαi inhibits adenylyl cyclase and lowers cAMP.

Which effector enzyme is activated by Gαq?

Phospholipase C beta.

What reaction is catalyzed by phospholipase C beta in hormone signaling?

It cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into DAG and IP3.

How do DAG and IP3 transmit the phospholipase C signal?

DAG activates protein kinase C, whereas IP3 binds receptors on the endoplasmic reticulum and promotes Ca2+ release.

What percentage of approved drugs was stated to target GPCR-mediated pathways?

Approximately 30%.

How do receptor tyrosine kinases transmit signals without a conventional second messenger?

They phosphorylate proteins and create docking sites that organize intracellular protein-protein interactions.

What structural feature distinguishes receptor tyrosine kinases from GPCRs?

Receptor tyrosine kinases have a single membrane-spanning region, whereas GPCRs have seven membrane-spanning helices.

What happens to many receptor tyrosine kinases when a ligand binds?

They form dimers or activate pre-existing dimers, leading to kinase activation and tyrosine phosphorylation.

What type of intracellular protein domain recognizes phosphorylated receptor tyrosines?

The Src homology 2 (SH2) domain.

How does a JAK-STAT-associated receptor differ from a receptor tyrosine kinase?

The receptor lacks intrinsic kinase activity and instead depends on an associated Janus kinase, such as JAK2.

Outline activation of the JAK2-STAT pathway.

Ligand binding changes receptor conformation; JAK2 activates by autophosphorylation; JAK2 phosphorylates receptor tyrosines; STAT proteins dock, become phosphorylated, and regulate transcription.

How do steroid and thyroid hormones alter target-cell function?

They cross the cell membrane, bind specific cytosolic or nuclear receptors, and regulate gene transcription and subsequent protein synthesis.

Why is the pituitary gland called the “master gland”?

Its hormones regulate other endocrine organs, including the thyroid gland, adrenal glands, ovaries, and testes.

Which hypothalamic releasing hormones regulate the anterior pituitary?

Thyrotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, and corticotropin-releasing hormone.

Which hypothalamic hormone in the slides inhibits anterior pituitary secretion?

Somatostatin.

How do the hypothalamus and posterior pituitary cooperate in hormone secretion?

The hypothalamus synthesizes oxytocin and antidiuretic hormone; they are transported to the posterior pituitary for storage and later release.

Which hormones are secreted by the anterior pituitary according to the slides?

Thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, growth hormone, prolactin, and POMC-derived peptides such as endorphins.

What is the structure of thyrotropin-releasing hormone?

A tripeptide with the sequence pyroglutamate-histidine-proline amide (pGlu-His-Pro-NH2).

Through which pathway does thyrotropin-releasing hormone signal in pituitary thyrotrophs?

It activates phospholipase C, generating IP3 and DAG and activating protein kinase C.

What two pituitary secretory effects are produced by thyrotropin-releasing hormone?

It increases thyroid-stimulating hormone synthesis and secretion and also stimulates prolactin release.

Who received the 1977 Nobel Prize associated with the discovery of thyrotropin-releasing hormone?

Roger Guillemin and Andrew Schally.

What is the structure of gonadotropin-releasing hormone?

A 10-amino-acid peptide with the sequence pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2.

Which pituitary cells are targeted by gonadotropin-releasing hormone?

Gonadotropes of the anterior pituitary.

How does gonadotropin-releasing hormone stimulate gonadotropin secretion?

Its cell-surface receptor activates phospholipase C, producing DAG, IP3, and increased Ca2+, followed by protein kinase C activation.

Which two hormones require gonadotropin-releasing hormone for their secretion?

Follicle-stimulating hormone and luteinizing hormone.

What is the size and principal action of growth hormone-releasing hormone?

It is a 44-amino-acid peptide that stimulates growth hormone synthesis and secretion from pituitary somatotrophs.

What is the main signaling pathway activated by the growth hormone-releasing hormone receptor?

The GPCR primarily activates adenylyl cyclase, increasing cAMP and activating protein kinase A; it can also activate phospholipase C.

What is the size of corticotropin-releasing hormone, and which cells does it target?

It is a 41-amino-acid peptide that targets anterior pituitary corticotrophs.

What hormones are released from corticotrophs in response to corticotropin-releasing hormone?

Adrenocorticotropic hormone and beta-endorphin.

How does corticotropin-releasing hormone increase intracellular signaling?

It binds a G protein-coupled receptor that activates adenylyl cyclase and increases cAMP.

What structural feature is present in somatostatin?

It is a 14-amino-acid peptide containing a disulfide bridge.

How does somatostatin reduce anterior pituitary secretion?

Its GPCR couples to Gαi, inhibiting adenylyl cyclase and decreasing cellular cAMP.

Which two anterior pituitary hormones are inhibited by somatostatin?

Growth hormone and thyroid-stimulating hormone.

How can a growth hormone-secreting pituitary adenoma produce abnormal skeletal growth?

Excess growth hormone stimulates the liver to produce excessive insulin-like growth factor 1, which increases bone and tissue growth.

How are anterior pituitary hormones grouped by chemical structure?

Glycoprotein hormones; the growth hormone-prolactin family; and pro-opiomelanocortin-derived peptide hormones.

Which anterior pituitary hormones are glycoproteins?

Thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone.

What are the structural features of anterior pituitary glycoprotein hormones?

They are synthesized as pre-prohormones, processed post-translationally, and contain noncovalently associated alpha and beta subunits.

What feature is shared by thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone?

They share an identical 92-amino-acid alpha subunit; their beta subunits provide hormone-specific biological activity.

What part of the common glycoprotein alpha subunit is important for receptor binding?

Its carboxyl-terminal pentapeptide.

Which signaling enzyme is activated by receptors for the pituitary glycoprotein hormones?

Adenylyl cyclase.

What is the overall function of thyroid-stimulating hormone?

It influences virtually every aspect of thyroid hormone biosynthesis and secretion.

What are the overall reproductive functions of follicle-stimulating hormone and luteinizing hormone?

They regulate gametogenesis and steroidogenesis in the gonads.

Which cells are principal targets of follicle-stimulating hormone?

Ovarian follicular cells and testicular Sertoli cells.

Which steroid-producing cells are stimulated by luteinizing hormone?

Corpus luteum cells produce progesterone, and testicular Leydig cells produce testosterone.

What are the principal structural facts about growth hormone?

It is a single 191-amino-acid polypeptide synthesized by anterior pituitary somatotrophs.

Which major pathways are activated downstream of the growth hormone receptor?

JAK2-STAT signaling, the mitogen-activated protein kinase pathway, and insulin receptor substrate-phosphoinositide 3-kinase signaling.

How does growth hormone receptor activation create docking sites for downstream proteins?

Growth hormone induces receptor dimerization, activating JAK2; JAK2 phosphorylates receptor tyrosines that recruit proteins such as STAT, SHC, and IRS.

What major physiological processes are supported by growth hormone-JAK2 signaling?

Growth, metabolism, and tissue repair.

What is pro-opiomelanocortin?

A 285-amino-acid precursor polypeptide that is cleaved into several biologically active peptide hormones.

Which products can be generated by pro-opiomelanocortin cleavage?

Adrenocorticotropic hormone, lipotropin, melanocyte-stimulating hormone, corticotropin-like intermediate peptide, and endorphins.

What is the size and principal endocrine effect of adrenocorticotropic hormone?

It is a 39-amino-acid peptide that acts through adenylyl cyclase and stimulates cortisol secretion by the adrenal gland.

How does adrenocorticotropic hormone promote cortisol biosynthesis through CREB?

cAMP activates protein kinase A, which activates cAMP response element-binding protein; CREB increases transcription of steroidogenic acute regulatory protein and steroidogenic enzymes.

What are the functions of steroidogenic acute regulatory protein and hormone-sensitive lipase in steroid production?

StAR promotes cholesterol transport into mitochondria, whereas hormone-sensitive lipase helps mobilize stored cholesterol for steroidogenesis.

Which pancreatic cells secrete insulin and glucagon?

Insulin is secreted by beta cells, whereas glucagon is secreted by alpha cells of the islets of Langerhans.

How do insulin and glucagon have opposing effects on blood glucose?

Insulin promotes glucose uptake and storage when blood glucose is high; glucagon promotes hepatic glycogen breakdown and glucose release when blood glucose is low.

Describe mature insulin’s polypeptide structure.

It contains an A chain of 21 amino acids and a B chain of 30 amino acids.

How are insulin’s A and B chains stabilized?

Two disulfide bridges connect the A and B chains, and an additional disulfide bridge occurs within the A chain.

What is the sequence of precursors involved in insulin biosynthesis?

Preproinsulin is processed to proinsulin, and removal of C-peptide produces mature insulin containing the A and B chains.

Why is C-peptide clinically useful even though it does not directly regulate glucose metabolism?

It reflects endogenous pancreatic beta-cell insulin production and helps distinguish type 1 from type 2 diabetes and endogenous from injected insulin.

What historical event marked the first therapeutic use of insulin?

On January 11, 1922, 14-year-old Leonard Thompson became the first person to receive an insulin injection for juvenile diabetes.

What contributions to insulin research were recognized by the 1923 and 1958 Nobel Prizes?

Frederick Banting and J. J. R. Macleod were recognized in 1923 for practical insulin extraction and medical application; Frederick Sanger was recognized in 1958 for determining insulin’s amino acid sequence.

Trace glucose-stimulated insulin secretion from glucose entry to granule exocytosis.

Increased glucose uptake and metabolism raise the ATP/ADP ratio; ATP-sensitive K+ channels close; reduced K+ efflux depolarizes the membrane; voltage-gated Ca2+ channels open; Ca2+ influx triggers insulin-granule exocytosis.

What type of receptor does insulin use?

A receptor tyrosine kinase.

Trace the principal insulin signaling pathway leading to GLUT4 movement.

Insulin binding activates receptor autophosphorylation; the receptor recruits and phosphorylates IRS; IRS activates phosphoinositide 3-kinase; this activates AKT; AKT promotes GLUT4 translocation to the plasma membrane.

How does GLUT4 translocation affect blood glucose?

Increased GLUT4 at the cell surface allows more glucose to enter insulin-responsive cells from the bloodstream.

What are the major structural and biosynthetic features of glucagon?

It is a 29-amino-acid polypeptide hormone produced by processing the larger precursor proglucagon.

What signaling pathway is activated when glucagon binds its hepatic receptor?

The receptor couples to Gαs, which activates adenylyl cyclase; cAMP rises, protein kinase A activates, and a phosphorylation cascade begins.

How does low blood glucose stimulate glucagon release from pancreatic alpha cells?

Reduced glucose uptake and metabolism lower the ATP/ADP ratio; KATP-channel activity supports electrical activity; voltage-gated Ca2+ channels open; Ca2+ influx triggers glucagon-granule exocytosis.

Trace glucagon signaling from cAMP formation to glycogen breakdown.

cAMP activates protein kinase A; protein kinase A activates phosphorylase kinase; phosphorylase kinase activates glycogen phosphorylase; glycogen phosphorylase breaks down glycogen.

How can calcium contribute to activation of glycogen breakdown independently of glucagon?

In contracting muscle, increased Ca2+ can activate phosphorylase kinase and thereby promote glycogen breakdown.

How does insulin reverse the glucagon-stimulated glycogenolysis pathway?

Insulin activates protein phosphatase 1, which dephosphorylates and inactivates enzymes in the glycogen-breakdown cascade.

Match the endocrine origins with these functions: posterior pituitary, thyroid, and parathyroid.

The posterior pituitary releases antidiuretic hormone for water conservation and oxytocin for uterine contraction and milk ejection; the thyroid produces thyroxine for metabolic-rate control; the parathyroid produces parathyroid hormone for calcium regulation.

Match the adrenal hormones with their principal functions shown in the slides.

Cortisol supports body preservation and stress adaptation; aldosterone promotes salt conservation; epinephrine mediates the stress response.

Which gonadal hormones and functions are listed in the slides?

The ovaries produce estradiol and progesterone, supporting female reproductive characteristics; the testes produce testosterone, supporting male characteristics.