Endocrine System I PDF

Introduction: Endocrine Function Endocrinology is the study of glands and the hormones they secrete Hormones are broadly classified in two groups: Water-soluble hormones Lipid-soluble hormones Hormones can travel through the bloodstream to target tissues to modulate functions of th...

Introduction: Endocrine Function Endocrinology is the study of glands and the hormones they secrete Hormones are broadly classified in two groups: Water-soluble hormones Lipid-soluble hormones Hormones can travel through the bloodstream to target tissues to modulate functions of those organs and tissues. They can also act on physically adjacent structures (paracrine function) or even on the cells that produced the hormone (autocrine function). Hormone levels are regulated by other stimulating and inhibiting hormones, by negative feedback, and by other homeostatic signals Hormone secretion follows specific time patterns Endocrine disorders often result from hormone excess or hormone deficiency  Water-Soluble Hormone Structures Norepinephrine Amine hormone Modified from amino acid tyrosine Hydrophilic, polar, unable to passively cross cell membrane Acts on G protein–coupled receptors  Water-Soluble Hormone Structures Oxytocin Short peptide chain Nine amino acids Hydrophilic, water-soluble Acts on G protein–coupled receptors  Water-Soluble Hormone Structures Growth hormone Long protein chain 190 amino acids Hydrophilic, water-soluble Acts on cytokine receptors Activates JAK-STAT signaling [involves cell surface receptors, Janus kinases (JAKs), and signal transducers and activator of transcription proteins (STATs)].  Lipid-Soluble Hormone Structures Steroid hormones Modified from cholesterol Hydrophobic, lipid-soluble Act on cytoplasmic and nuclear receptors  Modes of Hormone Signaling Endocrine Hormone is released from cell into bloodstream, travels through circulation to target cell Autocrine Cell has receptor for its own hormone Paracrine Hormone diffuses to neighboring cell which has a receptor for that hormone Neuroendocrine Neuron synthesizes hormone, action potentials release hormone from axon terminal into blood vessels  Cellular Mechanisms of Hormone Signaling: Hydrophilic Hormones Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5- trisphosphate (IP3), which serve as second messengers. Adenylyl cyclase catalizes the conversion of ATP to pyrophosphate and 3',5'-cyclic AMP (cAMP), which then serves as a regulatory signal.  Cellular Mechanisms of Hormone Signaling: Hydrophobic Mechanisms Cytoplasmic and nuclear (intracellular) receptors HRE, hormone-response element; mRNA, messenger RNA; NR, nuclear receptor.  Hormone-Binding Proteins Hydrophobic hormones travel in the circulation protected by hormone-binding proteins (usually made by the liver) This extends their half-life and keeps them in the circulation until reaching their target tissues Examples Corticosteroid-binding globulin Sex steroid-binding globulin Thyroxine-binding globulin Albumin (provides nonspecific binding of many hydrophobic substances) Hormones and Their Binding Proteins Hormone-Binding Proteins Hormone Binding Proteins Cortisol Corticosteroid-binding globulin Albumin Adrenal androgens Albumin Estrogen Albumin Sex hormone–binding globulin Progesterone Albumin Testosterone Sex hormone–binding globulin Thyroid hormones (T3 and T4) Thyroxine-binding globulin Transthyretin Albumin Insulin-like growth factor (IGF) Six different IGF binding proteins Growth hormone Growth hormone–binding protein  Objectives for the Endocrine System Part 1: the Hypothalamus and Pituitary Learn the anatomy and the pathophysiology of the hypothalamus and the anterior and posterior pituitary Become acquainted with the relationships between the hypothalamus and the pituitary Learn the hormones secreted by the hypothalamus, the anterior pituitary, and the posterior pituitary Describe the functions of the following cell types and the signals that affect them: Somatotrophs Thyrotrophs Gonadotrophs Corticotrophs Lactotrophs  Endocrine System Part 1: Hypothalamus and Pituitary Major functions of the hypothalamus include the following: Control of food intake, body temperature regulation, and sleep/wake cycles Influencing autonomic function through projections to the brainstem Producing posterior pituitary hormones arginine vasopressin (AVP) and oxytocin (OT) Producing releasing and inhibiting hormones that regulate anterior pituitary endocrine cells Primary hypothalamic disorders are rare, although meningitis and neoplasms may disrupt pituitary function  Hormones of the Hypothalamus Endocrine Source or Gland Hormone/Class Main Function of Hormone Hypothalamus Thyrotropin releasing Stimulates anterior hormone (TRH) pituitary thyrotropes to release TSH Peptide: 3 aa Somatostatin (SST) Inhibits release of several anterior pituitary Peptide: 14 or 28 aa hormones, including GH Kisspeptin Gonadotropin releasing Stimulates anterior hormone (GnRH) pituitary gonadotropes to release FSH and LH Peptide: 10 aa Corticotropin releasing Stimulates anterior hormone (CRH) pituitary corticotropes to release ACTH Peptide: 41 aa Growth hormone releasing Stimulates anterior hormone (GHRH) pituitary somatotropes to release GH Peptide: 44 aa  The Pituitary Major functions of the pituitary gland include the following: Secretion of growth hormone (GH) and prolactin (PRL) that influence target tissues Secretion of trophic hormones that stimulate target gland growth and hormone secretion Adrenocorticotrophic hormone (ACTH) Thyroid-stimulating hormone (TSH) Gonadotrophic hormones—luteinizing hormone (LH), follicle-stimulating hormone (FSH) Pituitary disorders include hormone-secreting neoplasms Hormones of the Thyroid stimulating hormone (TSH) Stimulates thyroid gland growth, promotes Glycoprotein: common α subunit—89 aa; unique β T4 and T3 synthesis and secretion Anterior pituitary subunit—112 aa Luteinizing hormone (LH) Females: stimulates ovarian sex steroid Glycoprotein: common α subunit—89 aa; unique β production, LH mid-cycle peak initiates ovulation subunit—115 aa Males: stimulates testis synthesis and secretion of testosterone Follicle-stimulating hormone (FSH) Females: stimulates ovarian early follicular cycle Glycoprotein: common α subunit—89 aa; unique β follicle development and preparation for subunit—115 aa ovulation Males: stimulates testis synthesis and secretion of testosterone Growth hormone (GH) Promotes growth of bones and organs; promotes Protein: 190 aa muscle protein synthesis, regulates metabolism of fat and liver Prolactin (PRL) Stimulates breast development and milk Protein: 198 aa production Adrenocorticotropic hormone (ACTH) Stimulates adrenal gland growth and hormone Protein: 39 aa secretion, particularly cortisol secretion And Posterior Vasopressin (AVP, antidiuretic hormone) Controls renal water retention to regulate blood Peptide: 9 aa volume and pressure, also functions as pituitary vasoconstrictor Oxytocin (OT) Stimulates uterine contraction, initiates milk Peptide: 9 aa ejection (let-down)  Other Hormones from the Pituitary: Melanocyte Stimulating Hormones MSHs are a family of peptide hormones and neuropeptides consisting of α-melanocyte- stimulating hormone (α-MSH), β-melanocyte- stimulating hormone (β-MSH), and γ-melanocyte- stimulating hormone (γ-MSH) produced by cells in the pars intermedia of the anterior lobe of the pituitary gland. The various forms of MSH are generated from different cleavages of the proopiomelanocortin protein, which also yields other important neuropeptides like adrenocorticotropic hormone. Melanocytes in skin make and secrete MSH in response to ultraviolet light, where it increases synthesis of melanin. Wikipedia, on Melanocyte-stimulating hormone  Endocrine Disorders of the Hypothalamus and Pituitary Hypocortisolism Secondary adrenal insufficiency Central hypercortisolism (Cushing Gonadotroph hypofunction disease) TSH deficiency Hypoprolactinemia TSH excess Hyperprolactinemia Diabetes insipidus Growth hormone deficiency Syndrome of inappropriate Growth hormone excess antidiuretic hormone (ADH) -Gigantism -Acromegaly  Hypothalamic-Pituitary-Target Gland Axes Hypothalamic neuroendocrine cells control pituitary hormone release Anterior pituitary cells control target gland hormone release Target gland hormones provide negative feedback to pituitary and hypothalamus  The Structure of the Hypothalamus The hypothalamus is found at the base of the brain on each side of the midline, surrounding the third ventricle and lying above the pituitary gland Several hypothalamic nuclei interact by synaptic connections, produce peptide neurotransmitters, and regulate sleep and waking (see Chapter 15, Nervous System), food intake, thirst, temperature regulation, and autonomic function Within several of the nuclei are the neuroendocrine cells with axons traveling in the pituitary stalk, where they release pituitary-controlling hormones  Relationship of Hypothalamus With Pituitary The hypothalamus lies below the thalamus along the midline at the base of the brain The infundibulum (pituitary stalk) connects the hypothalamus to the pituitary gland and has: Blood vessels that receive hypothalamic hormones Axons of AVP and OT neurons The posterior pituitary gland is the site of AVP and OT secretion The anterior pituitary contains the endocrine cells that secrete ACTH, TSH, LH, FSH, GH, and PRL  Hypothalamic/Posterior Pituitary Hormones Neuroendocrine cells in the paraventricular and supraoptic nuclei produce AVP and OT AVP secretion is stimulated by increased blood osmolality (detected by anterior hypothalamic osmoreceptors), and by hypotension and hypovolemia sensed by baroreceptors Angiotensin II receptors in the hypothalamus stimulate AVP secretion and also cause thirst Oxytocin secretion is stimulated during labor and during milk let-down when lactating  Hypothalamic Regulation of Energy Intake and Expenditure The hypothalamic arcuate and paraventricular nuclei contribute to regulation of food intake and energy expenditure, integrating both central and peripheral signals. ARC NPY/AgRP/GABA neurons promote food intake via projections to the PVN, acting on Y1 and Y5 receptors. ARC POMC neurons synthesize α-MSH, which, when released on PVN neurons, tends to inhibit food intake.  Hypothalamus and Pituitary Development Oral ectoderm folds upward, forming Rathke’s pouch Neural endoderm folds downward, below third ventricle Rathke’s pouch–derived tissue detaches from origin, forms anterior pituitary Neural endoderm forms pituitary stalk and posterior pituitary  Hypothalamus and Anterior Pituitary Regulation 1. Hypothalamic neuroendocrine cells project to capillary portal system of pituitary stalk 2. Anterior pituitary cells receive releasing and inhibiting hormones via portal veins and pituitary capillaries 3. Anterior pituitary cells secrete hormones into a second capillary bed within pituitary to travel to the systemic circulation  Targets of Anterior Pituitary Hormones Hormone Cell Type Percentage of Pituitary Targets Population Growth hormone (GH) Somatotroph 50 Liver, bone, muscle, adipose Adrenocorticotropic Corticotroph 15–20 Adrenal cortex hormone (ACTH) Luteinizing hormone (LH), Gonadotroph 10–15 Gonads Follicle-stimulating hormone (FSH) Prolactin (PRL) Lactotroph 10–25 Breasts, gonads Thyroid stimulating Thyrotroph