Endocrinology

Endocrine – glands secrete hormone into blood stream which acts at some distant tissue site. Pancreatic insulin (ß-cells) → muscle and fat

Exocrine – glands secrete non-hormone into ductal system for delivery to distant or adjacent site. Pancreatic enzymes (acinar cells) → intestinal contents

Paracrine – cells secrete hormone that acts directly on other nearby cells Testosterone (Leydig cells) → seminiferous tubules

Hormones are chemical messengers (signaling molecules) that are secreted directly into the blood, which carries them to organs and tissues of the body to exert their functions. There are many types of hormones that act on different aspects of bodily functions and processes.

Proteins or polypeptides: Hypothalamus, pituitary, pancreas, intestines, stomach, kidney, heart, parathyroids, liver. Steroids: Cholesterol derived Aromatic amino acid derivatives : Derived from tyrosine Catchecolamines (soluble, neurological actions)

-Proteins are water soluble and usually circulate without a carrier protein. -They interact with cell membrane receptors. EXAMPLE: -Inducing intracellular protein kinase action (G-coupled proteins) -Steroids are lipid soluble and transported bound to protein. -Internalized into cell, interact with nuclear receptors Modulate gene transcription

T3 and T4 (Thyroid hormones) -Transported bound to protein -Internalized into cell, interact with nuclear receptors (modulate gene transcription) Catecholamines (epinephrine, norepinephrine, dopamine) —-Soluble —-Mostly neurological actions

The Endocrine “Axis” Concept Hypothalamic releasing hormones stimulate pituitary secretion of trophic hormones Trophic hormones stimulate endocrine gland synthesis or secretion of primary hormone Endocrine hormone binds to specific receptors and effects action at target tissue(s)

Negative feedback: ———-An endocrine hormone acts upon either pituitary or hypothalamus to decrease secretion of the releasing factor or trophic hormone responsible for its secretion ———-More common Positive feedback: ———–An endocrine hormone acts upon either pituitary or hypothalamus to increase secretion of the releasing factor or trophic hormone responsible for its secretion ————Estradiol from developing follicle

Hypothalamus- Tertiary (rare) Pituitary- Secondary Tissues/organs- Primary

The midline base of the brain

Anterior pituitary (adeno-hypophysis) – gland nature ————Hypothalamic neurons secrete releasing factors into circulation which directly feeds pituitary Posterior pituitary (neuro-hypophysis) – neural nature ———–Hypothalamic neurons extend into neurohypophysis and secrete their hormones there

Synthesized in the hypothalamus and transported via axons for storage in posterior pituitary Arginine vasopressin (AVP, antidiuretic hormone, ADH) Cyclic nonapeptide Acts on kidney tubules to increase water reabsorption Vasoconstrictor Hypothalamic osmoreceptors & cardiac/carotid baroreceptors Oxytocin Cyclic nonapeptide differs from AVP by two amino acids Involved in lactation and parturition Milk letdown Uterine contraction Pitocin® – synthetic oxytocin to induce labor

Direct effector hormones • Growth hormone (GH, hGH) • Prolactin (Prl) Trophic hormones: • Adrenocorticotropic hormone (ACTH) • Follicle stimulating hormone (FSH) • Luteinizing hormone (LH) • Thyroid stimulating hormone (thyrotropin, TSH)

Somatotrophs (secrete GH) comprise over 1/3 of pituitary wt Stimulated by growth hormone releasing hormone (GHRH) – 44 aa peptide Inhibited by somatostatin – 14 or 28 aa peptide ——–Hypothalamus and pancreatic δ-cells

Secreted in pulsatile fashion (avg interval 2-3 hrs) —Greatest secretion during sleep —Spikes occur after meals and exercise —Blood GH may be undetectable between pulses ———Poor value of isolated GH blood samples

Anabolic: Increases protein synthesis, esp. in muscle Soft tissue, bone and cartilage growth Gluconeogenesis (glucogenic)

Stimulating lipolyisis.

insulin-like growth factor (IGFs, somatomedins, sulfation factor)

IGFs trophic

IGF-1 – most important IGF Previously known as somatomedin C Synthesized by the liver in response to GH Insulin structural homology Bound to IGF-binding protein 3 (IGF-BP3) Both IGF-1 and IGF-BP3 blood levels are positively correlated with GH secretion Blood levels are more stable than GH Preferred testing marker (± IGF-BP3) Measure by immunoassay (limited platforms)

Hypersecretion: Gigantism – GH excess during growth phase

Acromegaly – GH excess after growth complete commonly result from pituitary tumor

Hyposecretion: Pituitary dwarfism – not the same as achondroplasia Autosomal dominant FGFR3 mutation; homozygous fatal May result from tumors that interfere with GH secretion May also result from genetic defects in GHRH gene, GH gene, GH receptor, IGF-1 synthesis or receptor Adult deficiency Mental issues (vague) - social withdrawal, fatigue, … Osteoporosis Decreased lean body mass (muscle) Inc. total and LDL cholesterol