Ch 11: Endocrine System

Ch 11: Endocrine System

SLOs Describe the chemical nature of hormones and define the terms proand prepro-hormone. Explain mechanism of action of steroid and thyroid hormones Create chart to distinguish the the different classes of hormones (steroids, amines, poly peptides, and proteins and glycoproteins) according to how they are synthesized, stored, released, transported in blood, and cellular mechanisms of action. Predict the classification of an unknown hormone from knowledge of its synthesis, storage and release, transport in the blood, and cellular mechanism of action. Differentiate between anterior pituitary and posterior pituitary. List (full spellings and abbreviations) the hormones secreted by the anterior and posterior pituitary and identify the ones that have trophic effects. Explain how the hypothalamus regulates the anterior and posterior pituitary glands. Describe negative feedback inhibition in the regulation of hypothalamic and anterior pituitary hormones

Endocrine Glands and Hormones Review anatomy of ES / Major endocrine glands? What is a hormone? What is a neurohormone? : Study of hormones, their receptors, intracellular signaling pathways they invoke, diseases and conditions associated with them. Compare to Fig 11-1 Physiological processes controlled by hormones?

Chemical Classification of Hormones 3 main types: Steroids derived from,,, Secreted by and Amines, derived from tyrosine and tryptophan, T3 and T4, melatonin Polypeptides, Proteins and Glycoproteins ADH, insulin, GH, FSH and LH Where synthesized? Lipophilic or phobic? Where stored? How transported in blood?

Different classes of hormones differ on basis of synthesis, storage, release, transport and cellular mechanism of action Polar vs. non-polar Lipo vs. lipo

Biosynthetic Pathway for Steroid Hormones All derived from HO C D A B Cholesterol O OH Spermatic cord Testis Interstitial (Leydig) cells CH 3 C O CH 3 C O O Androstenedione O? Testosterone Seminiferous tubules HO Pregnenolone O Progesterone? Ovary HO CH 2 OH C O OH HO? OH Estradiol-17 Corpus luteum O Cortisol (hydrocortisone)? Ovary Follicles in ovary Adrenal cortex Fig 11-2

Tyrosine Derivatives I I I I I I I Compare to Fig 7-6

Pro-, Pre-, and Preprohormones Some hormones are 1 st produced as precursor molecules. They must be cut and sometimes spliced together to be active. E.g.: Insulin

Common Aspects of Neural & Endocrine Regulation Many similarities: Hormones and NTs both interact with specific Leads to change within cell Signal molecule is either removed or inactivated Multiple hormones can affect a single target simultaneously Three types of hormone interactions: Synergism Permissiveness Antagonism

Synergism Combined action of hormones may be more than just additive! 2 or more hormones work together to produce a particular effect Effects may be additive, as when E and NE each affect the heart in the same way. Effects may be complementary, as when each hormone contributes a different piece of an overall outcome.

Permissiveness One hormone makes target cell more responsive to a second hormone E.g.: Exposure to estrogen uterus more responsive to progesterone. Antagonism Insulin and glucagon both affect adipose tissue. 1)Insulin stimulates fat storage 2)Glucagon stimulates fat breakdown. Hormone Antagonists and Cancer: Tamoxifen as an exmaple of a SERM (see Clinical App, p. 325)

Effects of hormone concentrations on tissue response Hormone half-life Time for plasma concentration of a given amount of hormone to be reduced by half (mins to days) Liver removes most hormones from blood conversion to less active products Pharmacological hormone levels (?) binding to receptors of related hormones widespread side effects. E.g.: Steroid abuse Upregulation of receptors leads to priming effect Downregulation of receptors due to prolonged exposure to high concentrations of hormone. Desensitization can be avoided by releasing hormones in spurts = pulsatile secretion

MECHANISMS OF HORMONE ACTION Hormones bind to on or in cells. Binding is highly specific Hormone has high affinity Saturation occurs Location of hormone receptors? What is determining factor?

Nuclear Hormone Receptors for Steroid and Thyroid hormones Two regions on the receptor: 1)Ligand-binding domain for the hormone 2)DNA-binding domain for DNA These hormones act as transcription factors Fig11.4

Steroid hormone H Ligand-binding domain DNA-binding domain (a) Receptor protein for steroid hormone Half-sites Steroid Hormone DNA Receptors Hormoneresponse element Target gene Dimerization of receptor Steroid hormone H H Steroid hormone Fig. 11.5 (b) DNA Genetic transcription mrna

Compare to Fig11.4 There is also nongenomic action involving 2 nd messenger systems Which reaction is faster?

Coactivator and Corepressor......molecules often used in addition to the steroid hormone. They bind to nuclear receptor proteins at specific regions different effects of a given hormone in different cells

Cytoplasm Thyroid Hormone DNA Nucleus Action Receptor protein 4 5 mrna T 4 Carrier protein (TBG) 1 3 Binding protein mrna 6 Protein synthesis T 4 T 4 2 7 Thyroid hormone response Fig. 11.6 Blood Target cell

Hormones That Use 2 nd Messengers Catecholamines, polypeptides, proteins, and glycoproteins Cannot cross plasma membrane (?) bind to cell surface receptors Activate intracellular mediators called 2 nd messenger via Know adenylate (adenyl) cyclase / camp pathway only

Adenylate Cyclase (camp) System E and NE Fig. 11.8

PITUITARY GLAND Other name? Optic chiasma Hypothalamus Infundibulum Anterior lobe ( ) Posterior lobe ( ) Fig. 11.12

Neurohormones of Posterior Pituitary 2 neurohormones (?) Both are peptides (9 aa) transported in secretory vesicles via axonal transport Compare to Fig 11.13

Hormones of Anterior Pituitary 6 Hormones (names?) A Trophic hormone controls the secretion of another hormone. Target gland hypertrophies in response to trophic hormone. Hypothalamic trophic hormones and the hypothalamo-hypophyseal system

Review Table 11.6 and compare to Fig. 11.14

Feedback Control of Anterior Pituitary Final product regulates secretion of pituitary hormones: negative feedback inhibition Hypothalamus anterior pituitary target tissue axis Inhibition at pituitary level, inhibiting response to hypothalamic hormones. at hypothalamus level, inhibiting secretion of releasing hormones.

Negative Feedback Loops in Complex Endocrine Pathways Compare to Fig 11.16/17 Hypothalamus IC1 Ant. pituitary IC2 Endocrine gland IC3 Target tissue Hormones serve as negative feedback signals: Short-loop vs. long-loop negative feedback. Feedback patterns are important in diagnosis of ES pathologies

Higher Brain Controls Since hypothalamus receives input from higher brain regions, emotions can alter hormone secretion! Pituitary-gonad axis: At least 26 brain regions and olfactory neurons send axons to the GnRH-producing neurons. Pituitary-adrenal axis: Psychological stress influences CRH production Hot field: neuropsychophysiology