Endocrinology II Notes PDF

Hannah Love BIOS 25227 Endocrinology II Notes Lecture 1: Overview What distinguishes exocrine and endocrine glands? ​ Glands: organs that synthesize and secrete substances the body needs through ducts of directly into the bloodstream ​ Exocrine gland...

Hannah Love BIOS 25227 Endocrinology II Notes Lecture 1: Overview What distinguishes exocrine and endocrine glands? ​ Glands: organs that synthesize and secrete substances the body needs through ducts of directly into the bloodstream ​ Exocrine gland: (generally) ductal glands that secrete their products to the external surface of the body ○​ e.g. sweat glands, tear glands, digestive glands (because GI tract is “external” and contents will be excreted) ​ Endocrine gland: ductless glands that secrete products directly into the bloodstream ○​ Located at one place in the body, but releases hormone that circulates systematically throughout body Main endocrine systems are typically comprised of the hypothalamus, the pituitary, and a peripheral endocrine gland ​ Hypothalamus: integrates external and internal signals from body and environment and secretes hormones that stimulate or suppress the release of hormones in the pituitary gland ​ Pituitary gland: secretes hormones to stimulate adrenals, gonads, and thyroid, as well as its own end-product hormones, including growth hormone, antidiuretic hormone, prolactin, and oxytocin ○​ Anterior pituitary: secretes hormones like TSH, ACTH, LH, and FSH ○​ Posterior pituitary: stores and releases end-product hormones synthesized in the hypothalamus ​ Gonads: male and female reproductive glands that stimulate reproduction and phenotypic development during puberty ○​ Testes: secrete testosterone, which stimulates sperm production and other male characteristics ○​ Ovaries: secrete estrogen and progesterone, which dictate menstrual cycles and pregnancy ​ Adrenal cortex: secretes glucocorticoid in stress response, altering energy metabolism, as well as androgen hormone and aldosterone, weak testosterone-like substances that affect blood pressure and saline balance ​ Thyroid gland: secretes thyroxin, triiodothyronine, and calcitonin, which regulate basal metabolic rate, body heat, and bone growth ​ Parathyroid glands: secrete parathyroid hormone, which controls blood calcium levels  ​ Pancreas: in addition to exocrine digestive enzymes, secretes insulin and glucagon, which maintain plasma glucose homeostasis and regulate global energy storage, utilization, and mobilization ​ Adipose tissue/GI tract: secrete factors that affect central feeding behavior and peripheral insulin sensitivity in other tissues Endocrine systems maintain a “set point” through two main regulatory mechanisms 1.​ Opposing signals, in which different hormones have opposing effects—the relative ratio of the two opposing hormone levels ​ In the pancreas, insulin is secreted in response to hyperglycemia, promoting glucose storage, whereas glucagon is secreted in response to hypoglycemia, mobilizing stored glucose ​ In adipose tissue, leptin is secreted in response to blood glucose and insulin, decreasing hunger, whereas in the GI tract, ghrelin is secreted when the stomach is empty, increasing hunger 2.​ Feedback, in which the end-product hormone inhibits pituitary and hypothalamus to reduce hormone production ​ In HPT axis, thyroid hormone inhibits production of TRH in the hypothalamus and TSH in the pituitary ​ In HPG axis, gonadal steroids inhibit production of LH and FSH in the pituitary and GnRH in the hypothalamus  ○​ Exception is during pregnancy, in which the normally negative feedback loop becomes positive, with gonadal steroids increasing production in hypothalamus and pituitary ​ In HPA axis, cortisol inhibits production of ACTH in the pituitary and vasopressin (VP) and corticotropin-releasing hormone (CRH) in the hypothalamus Set point differs depending on environment ​ Hyde park vs. Cancun example: suppose 500 units of cortisol are being released—this is too much to maintain Cancun set point but too little for Hyde Park set point Hormone disorders can be primary, secondary, or tertiary, but in a healthcare setting, they are categorized as either primary or central ​ Primary: endocrine gland is defective, producing lower levels of end-product hormone; pituitary and hypothalamic hormones remain high because there is no feedback inhibition ​ Secondary: pituitary gland is defective, producing lower levels of pituitary hormone; this drives lower endocrine gland secretion, but hypothalamic secretion remains high due to lack of feedback inhibition ​ Tertiary: hypothalamus (PVN) is defective, producing lower levels of hypothalamic hormone; this drives lower pituitary and endocrine gland secretions ○​ Hypothalamic secretions are at very low levels and cannot be measured in the bloodstream—thus, cannot distinguish between secondary and tertiary disorders, so both are categorized as “central” ​ Hypothyroidism example: in primary hypothyroidism, thyroid hormone levels are low, but TSH and TRH levels remain high; in secondary hypothyroidism, thyroid hormone and TSH levels are low, but TRH remains high; in tertiary hypothyroidism, TRH, TSH, and thyroid hormone levels are low ○​ If endocrine gland and pituitary gland arrows are in different directions, primary; if endocrine gland and pituitary gland arrows are in the same direction, central Nervous system vs Endocrine System ​ Both integrate stimuli and responses to changes in external and internal environment, but nervous system makes point to point contacts using fast electrical signaling, whereas endocrine system broadcasts signals systemically through slow hormonal signaling ○​ Endocrine signaling is anatomically discontinuous, relying on systemic circulation of hormones through bloodstream ○​ Hormones: chemical messengers released by tissues in the body that regulate other cells, which are responsive if they contain a specific receptor for that hormone ​ Different effects in different parts of the body are due to differential receptor expression and activation/inactivation of hormone by local enzymes ​ Endocrine diseases can arise due to issues in hormone production or receptor expression Overview of hormonal activity ​ Autocrine actions: acts on same cells that released hormone ​ Paracrine action: released into extracellular fluid, acting on adjacent cells ​ Endocrine action: released into circulation and acts on distant target tissue ​ Neuroendocrine: released from neuron into circulation to act on distant target tissue ○​ E.g. posterior pituitary is direct neuroendocrine action, in which hypothalamic neurons release hormone into bloodstream via posterior pituitary ​ Hormones categorized into four structural groups: ○​ Peptides and proteins ○​ Amino acid derivatives ○​ Steroids ○​ Fatty acid derivatives/eicosanoids ​ Basic mechanism is as follows: secretory cell synthesizes, stores, and releases hormone into extracellular fluid, which reaches target cell, binding to specific receptor and triggering action in cell, and is then degraded and excreted ○​ Degradation and excretion regulate hormone levels in bloodstream ○​ Receptors provide several functions ​ Specification: only cells with the specific receptor will respond to a hormone ​ Amplification: allows small amount of hormone to produce large effect in target cell ​ Diversification: same hormone can have different effects in different cell types due to receptor subtypes and tissue-specific signaling pathways ​ Coordination: coordination of responses in different tissues and organs to maintain homeostasis  ​ Modulation: fine-tune or regulate hormone activity through differential expression or sensitivity ​ Desensitization: prolonged or repeated exposure to hormone decreases responsiveness ○​ Insulin and adrenaline example: insulin receptor (IR) usually decreases glycogen phosphorylase activity and increases glycogen synthase, promoting storage of glucose through glycogen; during fight or flight response, adrenaline activates cAMP pathway to increase glycogen phosphorylase and decrease glycogen synthase Early experiments in endocrinology ​ Berthold’s chicken experiment: castration of chicken resulted in caponization; castration and reimplantation/transplantation both resulted in normal male development ○​ Because testes functioned normally after all nerves were severed, there can be no specific nerves directing testicular function ○​ Testes extract rescued maleness—secretion from testes is what exerts effects ​ Parabiosis: castrated mouse surgically connected to circulatory system of normal mouse; testes of normal mouse increased in size to establish equilibrium ○​ LH and FSH levels rose in the castrated mouse due to removal of feedback inhibition, driving higher levels of LH and FSH in the normal mouse ○​ Gonads increased in size to create more endocrine hormone, producing enough gonadal secretion to establish equilibrium