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Chapter 14 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman.

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Presentation on theme: "Chapter 14 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman."— Presentation transcript:

1 Chapter 14 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman

2 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 2 Actions of estrogen to promote gamete transport. The decrease in pH and increase in glycogen in vaginal tissue promote sperm motility, and the decrease in viscosity of cervical mucus facilitates access to the uterine cavity. Increased contractions of the body of the uterus propel sperm toward the fallopian tubes where fertilization takes place. Ciliary activity of the infundibular epithelium and muscle contractions of the fallopian tubes propel the ovum and its associated cells toward the ampulla. (Drawing adapted from Netter, F.H. (1997) Atlas of Human Anatomy, 2nd ed., plate 346. Novartis, Hanover, NJ.) FIGURE 14.1

3 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 3 Relation between events of early pregnancy and steroid hormone concentrations in maternal blood. Estradiol and progesterone concentrations are redrawn from data given in Figure of Chapter 13. By the tenth day after the LH peak, there is sufficient human chorionic gonadotropin (hCG) to maintain and increase estrogen and progesterone production, which would otherwise decrease (dotted lines) at this time. FIGURE 14.2

4 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 4 A. Six-day-old blastocyst settles on endometrial surface. B. By the eighth day the blastocyst has begun to penetrate the endometrium. The expanding syncytiotrophoblast invades and destroys decidualized endometrial cells. C. By 12 days the blastocyst has completely embedded itself in the decidualized endometrium, and a clot or plug has formed to cover the site of entry. The trophoblast has continued to invade the endometrium and has eroded uterine capillaries and glands. A network of pools extravasated blood (lacunar network) has begun to form. (Adapted from Khong, T.Y. and Pearce J.M. (1987) Development and investigation of the placenta and its blood supply. In Lavery, J.P., ed. The Human Placenta: Clinical Perspectives, 26. Aspen Publishers, Rockville, MD.) FIGURE 14.3

5 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 5 Schematic representation of the human placenta. Placental villi are tree-like structures bathed in maternal blood in the intravillous space that is formed between the basal and chorionic plates. The insert shows a terminal villus consisting of fetal capillaries encased in a sheath of syncytiotrophoblast. The green arrows show the direction of blood flow into and out of the intravillous spaces. FIGURE 14.4

6 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 6 Maternal responses to hCG. FIGURE 14.5

7 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 7 Changes in plasma concentrations of pregnancy-related hormones during normal gestation. (Data for hCG, progesterone, estrogens, and hCS from Freinkel, N. and Metzger, B.E. (1992) Metabolic changes in pregnancy. In Williams Textbook of Endocrinology, 8th ed. Wilson, J. D. and Foster, D. W., eds. Saunders, Philadelphia. Graph for prolactin redrawn from Rigg, L.A., Lein, A., and Yen, S.C.C. (1977) Pattern of increase in circulating prolactin levels during human gestation. Am. J. Obstet. Gynecol. 129: 454–456. Graph for relaxin redrawn from data of Johnson, M.R., Abbas, A.A., Allman, A.C., Nicolaides, K.H., and Lightman, S.L. (1994) The regulation of plasma relaxin levels during human pregnancy. J. Endocrinol. 142: 261–265. Graphs for cortisol and ACTH are redrawn from data of Carr, R.B., Parker, C.R., Jr., Madden, J.D., MacDonald, P.C., and Porter, J.C. (1981) Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am. J. Obstet. Gynecol. 39: 416–422. Data for GH are reproduced from Fuglsang, J., Skjaerbaek, C., Espelund, U., Frystyk, S., Fisker, A., Flyvbjerg, A., and Ovesen, P. (2005) Ghrelin and its relationship to growth hormones during pregnancy. Clin. Endocrinol. (Oxf.) 62: 554–559.) FIGURE 14.6

8 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 8 Progesterone synthesis by the trophoblast. Cholesterol is taken up via low density lipoprotein (LDL) receptors and transferred to the inner mitochondrial matrix by constitutively expressed protein(s) where its C22-C27 side chain is removed by P450scc. Pregnenolone exits the mitochondria and is oxidized to progesterone by 3 -hydroxysteroid dehydrogenase (3 HSD). FIGURE 14.7

9 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 9 Biosynthesis of estrogens during pregnancy. Note that androgens formed in either the fetal or maternal adrenals are the precursors for all three estrogens, and that the placenta cannot convert progesterone to androgens. Hydroxylation of dehydroepiandrosterone sulfate on carbon 16 by the fetal liver gives rise to estriol, which is derived almost exclusively from fetal sources. Fetal androgens are secreted as sulfate esters and must first be converted to free androgens by the abundant placental sulfatase before conversion to estrogens by the enzyme P450aromatase (P450arom). 3 HSD = 3 -hydroxysteroid dehydrogenase. 17HSD = 17-hydroxysteroid dehydrogenase. FIGURE 14.8

10 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 10 Effects of estrogens on production of placental steroid hormones. By increasing uterine blood flow, and inducing low density lipoprotein (LDL) and P450 side chain cleavage (P450scc) enzyme, estrogens increase placental production of pregnenolone, which is used as substrate for androgen production in the fetal adrenals. Uptake of LDL from the maternal circulation may also transfer cholesterol to the fetal circulation. DHEAS = dehydroepiandrosterone sulfate. 16 -DHEAS = 16 hydroxy-dehydroepiandrosterone sulfate. CRH = corticotropin releasing hormone. ACTH = adrenocorticotropic hormone. hCG = human chorionic gonadotropin. FIGURE 14.9

11 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 11 Changes in peripheral resistance (Panel A), and cardiac output (Panel B), and plasma volume in normal pregnancies (C). (Data in panels A and B redrawn from Robson, S.H., Hunter, S., Boys, R.J., and Dunlap, W. (1989) Serial study of factors influencing changes in cardiac output during human pregnancy. Serial study of factors influencing changes in cardiac output during human pregnancy. Amer. J. Physiol. 256: H1060–H1065.) FIGURE 14.10

12 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 12 Relationship between plasma osmolality and ADH concentrations in eight women before and at the end of the third month of pregnancy. Arrows indicate plasma osmolality at which a conscious desire to drink (thirst) was experienced. (Drawn from the data of Davison, J.M., Shiells, E.A., Philips, P.R., and Lindheimer, M.D. (1988) Serial evaluation of vasopressin release and thirst in human pregnancy. J. Clin. Invest. 81: 798–806.) FIGURE 14.11

13 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 13 Summary of cardiovascular and renal changes in pregnancy. ERPF = effective renal plasma flow. GFR = glomerular filtration rate. FIGURE 14.12

14 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 14 The influence of placental hormones on maternal calcitropic hormones and calcium balance during pregnancy. Green arrows indicate stimulation; red arrows indicate inhibition. The effects of hCS, estrogens and IGF on bone (blue arrow) off set the calcium mobilizing effects of PTHrP, vitamin D and PTH (dashed green arrows). PTHrP = parathyroid hormone related peptide; hCS = human chorionic somatomammotropin; IGF = insulin-like growth factor II; PTH = parathyroid hormone. FIGURE 14.13

15 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 15 Summary of maternal adaptations to pregnancy. FIGURE 14.14

16 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 16 Effects of cortisol produced in the maternal and fetal adrenals in late pregnancy. By stimulating placental secretion of CRH (corticotropin releasing hormone) cortisol initiates direct and indirect (via the fetal and maternal pituitaries) positive feedback loops that enhance its own secretion and increases secretion of DHEA-S (dehydroepiandrosterone sulfate). In this way cortisol induced maturation of the fetus occurs simultaneously with increased production of estrogens, which prepare the uterus for parturition. ACTH = adrenocorticotropic hormone. FIGURE 14.15

17 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 17 Positive feedback cycles that contribute to initiation of parturition. CRH = corticotropin releasing hormone. Green arrows indicate stimulation; red arrows indicate inhibition. See text for details. FIGURE 14.16

18 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 18 Changes in plasma concentrations of corticotropin releasing hormone (CRH) and its binding protein (CRH-BP) in the days leading up to parturition. (From McLean, M., Bisits, A., Davies J., Woods, R. Lowry, P. and Smith, R. (1995) A placental clock controlling the length of human pregnancy. Nature Med. 1: 460–463.) FIGURE 14.17

19 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 19 A. Schematic view of the breast showing the relationship of the alveolar lobules and duct system. B. Arrangement of alveoli in a mammary lobule. C. Mammary alveolus consisting of milk-producing cells surrounded by a meshwork of contractile myoepithelial cells. Milk producing cells are targets of prolactin, while myoepithelial cells are targets of oxytocin. FIGURE 14.18

20 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 20 Relation of hormonal events in lactation to calcium metabolism. Secretion of prolactin inhibits hypothalamic secretion of the gonadotropin releasing hormone (GnRH) and stimulates secretion of the parathyroid hormone related peptide (PTHrP). PTHrP actions on bone, unopposed by estrogens, increase calcium (Ca2+) concentrations in blood and inhibit parathyroid hormone (PTH) secretion. Dashed arrows indicate stimulatory (green) or inhibitory (red) pathways that are blocked. FIGURE 14.19

21 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 21 Control of oxytocin secretion during lactation. FIGURE 14.20

22 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 22 Relation of blood oxytocin concentrations to suckling. Note that the initial rise in oxytocin preceded the initial period of suckling. (From McNeilly, A.S., Robinson, I.C.A., Houston, M.J. et al. (1983) Release of oxytocin and prolactin in response to suckling. Br. Med. J. 286: 257.) FIGURE 14.21

23 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 23 Plasma prolactin concentrations during nursing and anticipation of nursing. Note that although anticipation of nursing apparently resulted in oxytocin secretion, increased prolactin secretion did not occur until after suckling began. (From Noel, G.L., Suh, H.K., and Franz, A.G. (1974) Prolactin release during nursing and breast stimulation in postpartum and non-postpartum subjects. J. Clin. Endocrinol. Metab. 38: 413.) FIGURE 14.22

24 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 24 Control of prolactin secretion. Red arrows indicate inhibition and green arrows indicate stimulation. A physiological role for TRH (thyrotropin releasing hormone) and other postulated releasing hormones has not been established. Estradiol stimulates prolactin synthesis and may interfere with the inhibitory action of dopamine. FIGURE 14.23

25 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 25 Cellular events in the regulation of prolactin secretion. Steps in basal synthesis and secretion are indicated by the dotted black arrows. Effects of dopamine are shown by the red arrows. Effects of estradiol are shown in light blue. Gi and / = the subunits of the heterotrimeric inhibitory G protein. AC = adenylate cyclase. cAMP = cyclic adenosine monophosphate. PKA = protein kinase A. E2 = estradiol. ER = the estrogen receptor. PRL = prolactin. TRH (not shown) increases prolactin secretion through activation of its heptihelical receptor, which is coupled through G q to phospholipase C and caused release of inositol trisphosphate, diacylglyceride, and increased intracellular calcium. FIGURE 14.24

26 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 26 Around-the-clock prolactin concentrations in eight normal women. Acute elevation of prolactin level occurs shortly after onset of sleep and begins to decrease shortly before awakening. (From Yen, S.C., and Jaffe, R.B. (1999) Prolactin in human reproduction. In Reproductive Physiology, 4th ed., Yen, S.C. and Jaffe, R., eds., 268. Saunders, Philadelphia.) FIGURE 14.25


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