Chapter 11 Hormones Lecture map Hormones general biochemistry

Chapter 11 Hormones

Lecture map Hormones: - general biochemistry - endocrine organs and effects - anterior pituitary - hypothalamus - posterior pituitary - adrenal cortex - adrenal medulla

Lecture map Next: -endocrine organs and effects - thyroid - parathyroid - pancreas - pineal - thymus - placenta, gonads - adipose, skin, kidneys, heart, GI tract - autocrine system - endocrine signal transduction

HORMONES

Hormones Endocrine: into blood Exocrine: ducts Autocrine: same organ, same tissue Paracrine: same organ, different tissue

Endocrine hormones are in blood, so they reach all cells of the body. Each hormone only affects SOME cell types and tissues. - the cell has to express the particular receptor to “hear” the hormone signal.

Endocrine hormones Secretion hormone receptor Target cell

Hormone types Polar: Most hormones. Bind to receptor protein on pm. Lipophilic (nonpolar): Cross pm, act inside target cells. Steroid hormones and thyroid hormones. Can take orally, as pills.

Hormone types Hormones: Often amino acid derivatives or peptides. Steroid hormones are made from cholesterol.

Receptors Hormone receptors on target cells: Very specific Often high affinity (bond strongly) Integral mb proteins.

Effect of hormones Effect of hormone depends on… - blood levels - number of receptors on target cells - affinity of receptors for hormones

Effect of hormones Blood levels depend on: - gene expression - half-life of hormone - for lipophilic hormones: how much is bound to protein carriers

Regulation Endocrine hormones: secreted into blood, then removed by target organs and liver, converted to inactive form, and excreted. Half-life: Is general term for time required for the [molecule] to be reduced to half of reference level. This lecture: blood [hormone]. Way to quantify permanence of hormone. Minutes to hours, even days.

Regulation of receptor Upregulation: High or constant hormone levels can lead to more receptor proteins on target cells (usually through gene expression) and a greater response by the target cell.

Regulation of receptor Downregulation (desensitization): Prolonged, continuous exposure to high [hormone] can lead to diminished response (to same amount of hormone). One way: decrease in number of receptors on target cells. Through endocytosis, lysosomes, protein degradation. Pulsatile secretion of hormone (in spurts, over time) may prevent downregulation of receptor.

Regulation of hormone Hormone regulation: Active form= a certain configuration. Often inactive in blood.

Regulation of hormone Prohormone/prehormone: precursor molecule, usually inactive and can be modified (often cut) to become active. Preprohormone: precursor to prohormone!

Hormone effects Physiological range: [hormone] which produces normal responses. [pharmacological] are usually higher, can have different effects from physiological range.

Side effects of drugs Pharmacological drugs have side effects because: Hormones, neurotransmitters, etc. , regulate many targets, in many parts of the body. High doses may cause binding to other receptors (less specificity).

Hormonal Interactions Synergistic: enhance each other’s action. “two is better than one plus one!” Permissive: permits action of another hormone. Antagonistic: act in opposition; important for homeostasis!

PITUITARY GLAND

Pituitary Gland In diencephalon. Anterior lobe. Posterior lobe.

Anterior pituitary Derived from epithelial tissue. Controls growth of many other endocrine glands (“master gland”) - each known as an axis Trophic effects: High blood [hormone] causes target organ to hypertrophy. Low blood [hormone] causes target organ to atrophy.

Anterior pituitary Growth hormone (GH) -> many tissues, grow! Thyroid-stimulating hormone (TSH) -> thyroid secretes T 3, T 4 ACTH -> adrenal cortex to secrete glucocorticoids Prolactin -> milk Gonadotrophic hormones: FSH -> ovarian follicles, sperm cells LH -> ovulation; testosterone

Anterior Pituitary

Hypothalamus regulates the anterior pituitary! Physically linked, blood portal system. Hypothalamic hormones often called “(something) releasing hormones”

Hypothalamus

Hypothalamus Hypothalamic hormones -> Anterior pituitary hormones GHRH increases GH Somatostatin inhibits GH TRH increases TSH CRH increases ACTH PIH inhibits prolactin Gn. RH increases FSH and LH

Regulation of Anterior Pituitary Mostly through negative feedback inhibition from target organs to hypothalamus or directly to anterior pituitary. Ex: TSH -> T 4 ---l TSH

Regulation of Anterior Pituitary So, once a certain amount of hormones are made, they shut off the system producing them!

Antagonistic effectors GHRH -> GH l- Somatostatin -l GH TRH -> TSH -> T 4 -l TSH, TRH CRH -> ACTH -> Glucocorticoids -l CRH PRH -> Prolactin PIH -l Prolactin

Antagonistic effectors Gn. RH -> FSH, LH Gonadal hormones -l FSH, LH Estogen can inhibit, or stimulate, depending on levels! Some levels even stimulate synthesis of FSH, LH, but prevent release. (p. 932) Testosterone -l Gn. RH, FSH, LH

Hormones Estrogens are a family of several hormones. (Testosterone is one hormone. ) Male brains have an enzyme that turns testosterone into estrogens! (note: PIH is dopamine!)

Hormones GH: - “fountain of youth? !? ” - secreted mostly in adolescence - too much: gigantism, acromegaly - too little: pituitary dwarfism - stimulates uptake of amino acids into cells

Hormones Note: stress -> CRH -> ACTH -> glucocorticoids

Posterior pituitary Formed by downgrowth of the brain during fetal development. Under direct neural control. Nerve fibers extend through the infundibulum.

Posterior pituitary Stores and releases 2 hormones that are produced in the hypothalamus: - Antidiuretic hormone (ADH) - Oxytocin

Posterior pituitary Antidiuretic hormone (ADH): - aka vasopressin - promotes the retention of H 20 by the kidneys

Posterior pituitary Oxytocin: - stimulates contractions of the uterus during parturition. - stimulates contractions of the mammary gland alveoli for milk-ejection reflex. - bonding with baby? ! - orgasm?

Posterior Pituitary

ADRENAL GLANDS

Adrenal Glands Paired organs that cap the kidneys. Each: outer cortex and inner medulla.

Adrenal cortex: - stimulated by ACTH. - secretes corticosteroids - different regions secrete different hormones. - all made from cholesterol.

Adrenal Cortex Corticosteroids include: - mineralocorticoids: - glucocorticoids - gonadocorticoids

Adrenal Cortex Mineralocorticoids: - aldosterone - targets kidneys - affects Na+ and K+ balance - stimulates transcription of Na+/K+ ATPase pump! - more aldosterone -> more Na+, water in body - stress -> CRH -> ACTH -> aldosterone -> retain fluid -> high blood pressure!

Adrenal Cortex Glucocorticoids (gc) - cortisol (aka hydrocortisone) - metabolism, more glucose in blood - stress -> large increase in gc - pharmacologically: suppress inflammation, asthma, rheumatoid arthitis

Adrenal Cortex Gonadocorticoids: - aka sex steroids - include DHEA (precursor for estrogen, testosterone) - not well understood http: //www. quackwatch. org/01 Quackery. Related. Topics/dhea. html

Adrenal Cortex

Adrenal Medulla Adrenal medulla: Derived from embryonic neural crest ectoderm (same tissue that produces the sympathetic ganglia). Controlled by preganglionic sympathetic innervation (is like a postganglionic neuron!) Secretes adrenaline (aka epenephrine) (also secretes norepenephrine)

Sympathetic response Adrenaline: part of sympathetic response to a threat! “fight or flight” Also, fear, sex Also: tend and befriend Triggered by physical and emotional/psychological stress: body responds similarly to “bear in woods” or to stressful words.

Sympathetic response: Body changes to short-term, muscular focus. Increased respiratory rate, heart rate, blood glucose. Decreased digestion, immune system, memory, analytical thinking.

Sympathetic response Adrenaline: - used medically to stimulate heart or to dilate bronchioles (in an asthma attack) when locally administered through an inhaler

Chronic stress: Chronic activation of sympathetic response. Harder to turn off the sympathetic response, Cardiovascular damage, attentuated immune defenses… Why zebras don’t get ulcers. Robert M. Sapolsky

Parasympathetic response: Turn on by - deep breaths… - “count to ten!” or do a math problem… - meditate, yoga…