Overview Endocrine Function

Hypothalamus-Pituitary Axis

Bio 328 Spring 2013

Ruth Clark, P.T., Ph.D.

I. Introduction: A. Definitions

Endocrine Gland/Tissue

Hormone

Receptor

Target cell

Paracrine

Autocrine

B. Major Functions of the Endocrine System 1) Fetal:

2) Childhood:

3) Reproduction:

4) Physiological stress:

5) Homeostasis:

C. Cell Response-Signal Transduction 1. Time scale of biological response to hormone varies: seconds minuteshours days

2. Genomic versus nongenomic cell response a. genomic response: stimulation of transcription and translation

b. nongenomic responses

Overview Endocrine Function

Hypothalamus-Pituitary Axis

2

II. Hormone Structural Classes A. Hormones Synthesized from amino acids: tyrosine and tryptophan

Tyrosine: Dopamine, Norepinephrine, Epinephrine, Thyroid hormone Tryptophan: Serotonin (GI mucosal cells and cells in large bronchi)

B. Peptide/Protein Hormones: largest class of hormones 1. Synthesis: Preprohormone Prohormone stored in vesicle secretion of hormone (see figure 11-3 in Vander’s Physiology) 2. Mechanisms of Action

Variety of signal transduction mechanisms For review: Vander’s Human Physiology text, 12th edition Review figures and Table 5-2 for overview of receptor mechanisms C. Steroid Hormones 1. Steroid hormones: synthesized from cholesterol a. Gonadal hormones; Androgens, Estrogens, Progestins b. Adrenal cortex

Mineralocorticoid: Aldosterone from the Zona glomuerulosa Glucocorticoids: Cortisol from the Zona fasiculata and reticularis Androgens from the Zona fasiculata and reticularis

c. Placental hormones produced during pregnancy d. Vitamin D3: 1,25-dihydroxyvitamin D 2. Synthesis of steroid hormones Key enzymes and steps in the synthesis of steroid hormone.

o LDL receptor o Adenylyl cyclase and protein kinase A o Cholesterol esterase o P450 enzymes

Schematic figure of synthetic steps(see figure 11-5 in Vander’s Physiology) 3. Mechanism of Action of Steroid Hormones

Steroid hormone binds to intracellular receptors in the cytosol or nucleus

Active hormone-receptor complex binds to specific DNA sequences called steroid response elements SREs

Overview Endocrine Function

Hypothalamus-Pituitary Axis

3

D. Homeostasis of Hormone Concentration: Synthesis = Degradation/Inactivation 1. Stimuli for secretion: a. ions b. nutrients c. neurotransmitters d. other hormones 2. Secreted hormone increase in plasma hormone level a. target cell response b. sometimes hormone is metabolized to active form c. some hormone may be metabolized to inactive form d. excreted 3. Hormone Transport in the Blood E. Other hormone effects

1. Tropic hormones: stimulate secretion of target gland hormone; e.g., anterior pituitary hormones have both tropic and trophic effects on target cells

2. Permissive effects: presence of one hormone stimulates the action of other

hormones; e.g., thyroid affects on epinephrine and norepinephrine, cortisol effects

Overview Endocrine Function

Hypothalamus-Pituitary Axis

4

III. Hypothalamic-Pituitary-Target Gland Axis

A. Hypothalamus controls secretion of Anterior Pituitary Hormones via secretion of hypothalamic hormones (synthesized in neurons in the hypothalamus) into the hypothalamo-pituitary portal vessels

These hypothalamic hormones travel via the portal vessels to specific target cells in the anterior pituitary.

1. Corticotropin-releasing hormone (CRH) stimulate secretion ACTH

2. Gonadotropin-releasing hormone (GnRH) stimulate secretion FSH/LH

3. Growth hormone releasing hormone (GHRH) stimulate secretion GH

4. Somatostatin (Growth hormone inhibitory hormone) inhibits secretion GH

5. Thyrotropin-releasing hormone (TRH) stimulate secretion TSH

6. Dopamine (Prolactin-inhibiting hormone) inhibits secretion prolactin

B. Posterior Pituitary: Hypothalamic neurons synthesize vasopression and Oxytocin. These hormones are transported via axonal transport to neuron terminal in the posterior pituitary. 1. ADH (vasopressin): major target cells are the renal tubule cells where ADH stimulates the insertion of water channels (aquaporin) into renal tubule cells. ADH also stimulates contraction of vascular smooth muscle and thus the pressor or vasoconstriction function of ADH

2. Oxytocin major target cells are the female breast for milk ejection, Oxytocin also stimulates uterine contractions

C. Hormones synthesized & secreted from the Anterior Pituitary exert tropic effect on target cells

1. Follicle-stimulating hormone/ Luteinizing hormone (FSH/LH) gonads Female gonad produces estradiol and progesterone Male gonad produces testosterone 2. Growth Hormone Liver and body’s cellsIGF-1 3. Thyroid stimulating hormone (TSH) thyroid gland T3/T4 4. Prolactin breast 5. ACTH Adrenal Cortexsecretion of Glucocorticoids (Refer to figures 11-13, 11-15, 11-16, 11-17, 11-18, 11-20 in Vander’s Physiology)

Overview Endocrine Function

Hypothalamus-Pituitary Axis

5

D. Hypothalamic—Pituitary—Target Gland Feedback

1. Long loop feedback regulation

2. Short loop feedback regulation

3. Positive versus Negative feedback IV. Categories of Endocrine Disorders

A. Alterations in secretion 1. Hyposecretion

2. Hypersecretion B Altered responsiveness of the target cell

1. Hyporesponsiveness

2. Hyperresponsiveness