LECTURE 2 SECTION 2 ENDOCRINOLOGY INTRODUCTION Cell to Cell Communication Locally Direct Physical Contact Chemical or Electrical Contact At Distance Chemical or Electrical Contact nervous system circulatory system Hormones (classical definition) Chemical agents synthesized and secreted by specialized ductless glands and carried by the blood stream to specific target tissues where they evoke physiological adjustments Glands Endocrine glands -- ductless glands which secrete directly into blood stream (have a larger blood supply then other glands) http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (1 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Exocrine glands-- ducted glands which secrete externally, not into the blood stream Receptor sites--specific sites located on the cell membrane or within the cell which have a high affinity for a specific hormone (lock and key) General properties of hormones Effect specialized tissues containing receptors Do not initiate reactions Are not chemically unique Have variable speeds of reaction Active at very low concentrations -9 (10 grams = nanograms (ng) or ppb) (10-12 grams = picograms(pg) or ppt) Reproductive Hormone Classes Neurohormones -- peptides Gonadotropic hormones -- proteins Gonadal hormones -- steroids, peptides & proteins Uterine and placental hormones -- proteins, steroids & lipids HORMONES FROM ANTERIOR PITUITARY (AP) Gonadotropins http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (2 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Follicle stimulating hormone (FSH) Glycoprotein hormone MW - 32,000 t½ - 2 to 2½ hours Structure About 210 amino acids in a and ß subunits Actions in female Stimulates Follicle growth Stimulates Estrogen production (in conjunction with LH) Stimulates Inhibin production Actions in male Stimulates Spermiogenesis Stimulates Inhibin production Stimulates Androgen-binding protein Uses by Man Stimulation of follicular development to induce multiple ovulations Luteinizing hormone (LH) Glycoprotein hormone http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (3 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 MW - 30,000 t½ - 30 min Structure About 215 amino acids in a and ß subunits Actions in female Maturation of follicle Ovulation Corpus luteum (CL) formation Progesterone production (luteotropic effect) Actions in male Testosterone production Uses Induces ovulation Treatment of cystic ovaries Human Menopausal Gonadotropins (hMG) Recovered from urine of menopausal women Both LH and FSH units (1:1) Use superovulation http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (4 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Prolactin (Prl) Not a "gonadotropin" in domestic animals Protein hormone MW - 24,000 Structure About 198 amino acids Actions in female Milk synthesis Development of mammary gland Maternal behavior Adrenocorticotropic hormone (ACTH) Polypeptide hormone (MW - 4,500) Action in female and male Release of glucocorticoids from adrenal gland HORMONES FROM OVARY Estrogens Major estrogens Estradiol-17 beta (E2ß) Estrone (E1) http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (5 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Estriol (E3) Estradiol-17 alpha (E2a) Structure (FIGURE 1) Steroid hormones 18 carbons MW for estrogens varies (272 to 288) Site of production Theca and granulosa cells in follicle Actions Estrus Uterine contractions Positive and negative feedback on gonadotropins Duct growth of mammary gland Secondary sex characteristics Growth of female reproductive tract Calcium uptake and ossification of bones Anabolic effects Uses http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (6 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Induction of behavioral estrus Induction of uterine contractions Promotes growth in domestic animals Birth control pills for humans Progestins or Progestogens Major progestogens Progesterone (P4) 17a-Hydroxyprogesterone 20ß-dihydroprogesterone Structure (FIGURE 1) Steroid hormones 21 carbons MW for progesterone - 314 Site of production Luteal cells of corpus luteum Actions Maintenance of pregnancy Inhibits uterine contractions Inhibition of estrus http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (7 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Alveolar growth of mammary glands Secondary sex characteristics Growth of female reproductive tract Stimulates endometrial secretion Negative feedback on gonadotropins Uses Prevents abortion Birth control pills Synchronization of estrus and ovulation Inhibin (Folliculostatin) Structure Glycoprotein hormone MW - 32,000 Contains a and ß subunits Site of production Granulosa cells of follicle Found in follicular fluid Action Selectively suppresses release of FSH from AP http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (8 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Relaxin Structure Polypeptide hormone MW - 5,700 to 6,500 Site of production Luteal cells of corpus luteum during pregnancy Also produced by placenta and uterus Actions Acts on tissues after presensitization to estrogens Relaxation of pelvic ligaments Softens connective tissue in uterine muscles Softens connective tissue of cervix at parturition HORMONES FROM TESTIS Androgens Major androgens Testosterone (T) Androstenedione (A) Dihydrotestosterone (DHT) Structure (FIGURE 1) http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (9 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Steroid hormones 19 carbons MW for testosterone - 288 Site of production Leydig cells of testes Actions Spermatocytogenesis Male sexual behavior (libido) Secondary sex characteristics Maintains accessory sex organs Negative feedback on gonadotropins anabolic effects Uses Prepare teaser animals for estrous detection Improve performance in feedlot animals Inhibin Structure Glycoprotein hormone MW - 32,000 http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (10 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Contains a and ß subunits Site of production Sertoli cells of testes Function Selectively suppresses release of FSH from AP HORMONES FROM PLACENTA Estrogens -- Same as for ovary Progestins -- Same as for ovary Relaxin -- Same as for ovary Human chorionic gonadotropin (hCG) Structure Glycoprotein hormone MW - 40,000 a and ß subunits with 237 amino acids Site of production Syncytiotrophoblastic cells of placenta Actions Converts CL of menstrual cycle to CL of pregnancy http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (11 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 LH-like Uses Human pregnancy test kits Induces ovulation Source -- Urine of pregnant women Treatment of cystic ovaries Pregnant mare serum gonadotropin (PMSG or eCG) Structure Glycoprotein hormone MW - 28,000 t½ - several days Site of production Endometrial cups of mare's placenta Actions Formation of accessory CL in mare during pregnancy FSH-like in domestic animals other than mare Use Stimulates excessive follicular development in domestic animals other than mare Source -- Isolated from mare's serum http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (12 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Placental lactogen Structure Protein hormone MW - 22,000 to 23,000 About 192 amino acids Similar to prolactin and growth hormone Highest concentrations Last trimester of pregnancy Higher concentrations in dairy than beef cows Site of production Placenta Possible functions Development of mammary gland for milk production Regulation of maternal nutrients to fetus Regulation of fetal growth Protein B Structure Protein hormone t½ - 7 days http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (13 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Site of production Placenta of bovine and ovine Function Unknown Possible use Pregnancy test substance in cow and ewe (Detectable 22 days after conception in cow) HORMONES FROM UTERUS Relaxin Same as for ovary Prostaglandin (PG) F2_ Structure Lipid hormone (Figure 2) 20 carbons Arachidonic acid precursor MW - 355 Source Endometrial cells of uterus Also produced by vesicular glands of male http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (14 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Actions Regression of CL (luteolytic) Causes constriction of blood vessels Stimulates smooth muscle contraction for sperm transport, ovum transport, parturition and ovulation Stimulates gonadotropin release Practical uses Synchronization of estrus and ovulation in cows and mares Luteolytic effect on CL Abortion in feedlot heifers Aids in treating uterine infections in dairy cows PGF2_ compounds commercially available Lutalyse (Upjohn) Estrumate (Haver-Lockhart) Bovilene (Syntex) Equimate (ICI United States) Prostaglandin (PG) E2 Structure http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (15 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Lipid hormone 20 carbons Arachidonic acid precursor MW - 352 Source Same as PGF2_ Actions Smooth muscle stimulator Effects on CL are opposite to that of PGF2_ Antiluteolytic action may be a factor in maintenance of CL during pregnancy Involved in process of ovulation Involved in gamete transport HORMONES FROM ADRENAL GLAND Glucocorticoids Cortisol Structure Steroid hormone MW - 362 Site of production http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (16 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 Adrenal cortex Actions Initiation of parturition Synergizes with prolactin to initiate milk synthesis Reduces inflammation OTHER HORMONES Compudose Implant Contains estradiol-17ß Increases weight gain and feed efficiency For steers Synovex-H Implant of estradiol benzoate and testosterone propionate Increases weight gain and feed efficiency For heifers Synovex-S Implant of estradiol benzoate and progesterone Increases weight gain and feed efficiency http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (17 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 For steers STEER-oid Generic equivalent implant to Synovex-S Diethylstilbestrol Commonly called DES (Figure 3) No longer approved by FDA Anabolic, promotes nitrogen retention Increases weight gain and feed efficiency Ralgro Zeranol (Figure 3) Plant extract with estrogen activity Binds to estradiol receptor Increases weight gain and feed efficiency Norgestomet Trade name is Syncro-Mate-B (Figure 3) Progestin compound for synchronization of estrus and ovulation in cows Melengestrol Acetate Progestin compound (Figure 3) http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (18 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 For use in feedlot heifers to suppress estrus Increases weight gain and feed efficiency Regumate Progestin compound (Altrenogest) Suppresses estrus in mares MECHANISM OF ACTION OF HORMONES Gonadotropins (Figure 4) Gonadotropic hormone (first messenger) binds to membrane receptor Receptor activates adenylate cyclase which converts ATP to cyclic AMP (cAMP) cAMP (second messenger) stimulates steroidproducing enzymes to produce estrogen, progestogen or androgen Hormone secreted into blood stream Steroids (Figure 5) Steroid hormone (S) passes through cell membrane Steroid binds to a protein receptor (R) in cytoplasm Steroid-receptor complex translocates to nucleus Stimulates synthesis of mRNA Messenger RNA translocates to cytoplasm Synthesis of specific proteins http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (19 of 20) [6/10/2008 11:51:03 AM] LECTURE 2 New proteins responsible for action of steroid hormone on target tissue Back to ASFT 3401 Index http://www.ttuhsc.edu/som/obgyn/faculty/Prien/Lecture%20notes/ASFT3401/endocrin.htm (20 of 20) [6/10/2008 11:51:03 AM]