Hormonal physiology of Pregnancy and lactation

1. Hormonal physiology of Pregnancy and lactation Class: II M.Sc., Unit: 4 Prepared by: A. Benno Susai Department of Biochemistry, SJC, Trichy

2. Female Reproductive System • Uterus: • Has 3 layers: • Perimetrium: • Outer layer of connective tissue. • Myometrium: • Smooth muscle layer. • Endometrium: • Inner layer of stratified, squamous, nonkeratinized epithelium. • Shed during menstruation. • Vagina: • Cervical mucus plug. Department of Biochemistry, SJC, Trichy

3. Oogenesis • Primary Oocytes form at 3 months during fetal development • 2 million primary oocytes by birth in prophase of first meiotic division • Maturation increases size • First meiotic division few hrs before ovulation • Second after fertilization Department of Biochemistry, SJC, Trichy

4. Oogenesis 2 • Division produces unequal mass of cells most food goes to ovum and none to polar body. • All polar bodies die eventually. • Oocyte + specialized cells=follicle: Nourish ovum and secrete estrogens • Mature follicle bursts releasing ovum. • Many follicles enlarge but only one bursts. Department of Biochemistry, SJC, Trichy

5. Ovarian Cycle • ovaries contain 6-7 million oogonia. • Oogenesis arrested in prophase of 1st meiotic division (primary oocyte). • Apoptosis occurs: • 2 million primary oocytes at birth. • 400,000 primary oocytes at puberty. • 400 oocytes ovulated during the reproductive years. Insert fig. 20.30 Department of Biochemistry, SJC, Trichy

6. Ovarian Cycle • Primary oocytes are contained in primary follicles. • FSH stimulates granulosa cell growth. • Develop into secondary follicles. • Fusion of its vesicles to form the antrum. • Mature graafian follicle. • 1st meiotic division completed (secondary oocyte). • Polar body fragments. Insert fig. 20.32 Department of Biochemistry, SJC, Trichy

7. Ovarian Cycle • Secondary oocyte confined to graffian follicle. • Arrested at metaphase II. • Under FSH stimulation: • Theca cells secrete testosterone. • Granulosa cells contain the enzyme aromatase to convert testosterone into estrogen. • Granulosa cells form a ring (corona radiata) around oocyte and form mound (cumullus oophorus). • Between oocyte and corona radiata is zona pellucida. • Provides barrier to the sperm to fertilize the egg. Department of Biochemistry, SJC, Trichy

8. Ovulation • One graafian follicle forms bulge on surface of ovary. • Extrudes secondary oocyte into the uterine tube. • LH causes the empty follicle to become corpus luteum which secretes: • Progesterone and estrogen. • If not fertilized, becomes corpus albicans. Department of Biochemistry, SJC, Trichy

9. Luteal Phase • LH stimulates formation of the empty follicle into corpus luteum. • Corpus luteum secretes: • Progesterone: • Plasma concentration rapidly rises. • Exerts negative feedback on LH and FSH. • Inhibin: • Suppresses FSH secretion. • Inhibin production decreases towards end of luteal phase. Department of Biochemistry, SJC, Trichy

10. Luteal Phase (continued) • Corpus luteum regresses unless fertilization occurs: • Estradiol decreases. • Progesterone decreases. • Withdrawal of estradiol and progesterone cause menstruation to occur. Department of Biochemistry, SJC, Trichy

11. Cycle of Ovulation and Menstruation Insert fig. 20.35 Department of Biochemistry, SJC, Trichy

12. Cyclic Changes in the Endometrium • Proliferative Phase: • Ovary is in follicular phase. • Estradiol stimulates growth of endometrium of stratum functionale. • Spiral arteries develop. • Estradiol: • Stimulate production of receptor proteins for progesterone. Department of Biochemistry, SJC, Trichy

13. Cyclic Changes in the Endometrium (continued) • Secretory phase: • Ovary is in luteal phase. • Progesterone stimulates development of uterine glands, which become engorged with glycogen. • Endometrium becomes thick, vascular, and spongy. • Cervical mucus thickens and becomes sticky. Department of Biochemistry, SJC, Trichy

14. Cyclic Changes in the Endometrium (continued) • Menstrual phase: • Progesterone withdrawl causes constriction of spiral arteries. • Necrosis and sloughing of endometrium occurs. • Lasts 1-5 days. Department of Biochemistry, SJC, Trichy

15. Contraceptive Methods • Contraceptive pill: • Synthetic estrogen combined with synthetic progesterone pills are taken once each day for 3 weeks after the last day of menstruation. • Negative feedback inhibits ovulation. • Placebo pill taken on the 4th week permits menstruation. • Rhythm method: • Women measure oral basal body temperature upon awakening daily. • On day of LH surge, there is a slight drop in basal body temperature. Department of Biochemistry, SJC, Trichy

16. Menopause • Cessation of ovarian activity and menstruation. • Age ~ 50 years. • Ovaries are depleted of follicles. • Estradiol and inhibin withdrawl causes hot flashes, and atrophy of the vaginal wall. • LH and FSH increase. Department of Biochemistry, SJC, Trichy

17. Fertilization • Ejaculation 300 million sperm, 100 reach (uterine) fallopian tube. • Capacitation occurs. • Fertilization occurs in the uterine tubes. • Acrosome of sperm contains hyaluronidase, an enzyme that digests a channel through zona pellucida. • Sperm fuses with ovum cell membrane. Insert 20.39 Department of Biochemistry, SJC, Trichy

18. Fertilization (continued) • As fertilization occurs, secondary oocyte completes 2nd meiotic division. • Sperm enters ovum cytoplasm. • Ovum nuclear membrane disappears, zygote formed. • Centrosome of zygote is derived from sperm cell. Insert fig. 20.41 Department of Biochemistry, SJC, Trichy

19. Cleavage and Blastocyst Formation • Cleavage: • 30-36 hrs. after fertilization, the zygote divides by mitosis. • About 50-60 hours after fertilization, the early embryo develops into morula. • Blastocyst develops: • Inner cell mass • Fetus. • Surrounding chorion: • Trophoblasts form placenta. Insert fig. 20.43 Department of Biochemistry, SJC, Trichy

20. Implantation • 6th day after fertilization, blastocyst attaches to uterine wall. • Trophoblast cells produce enzymes that allow blastocyst to burrow into endometrium. Insert fig. 20.45 (Chorion) Department of Biochemistry, SJC, Trichy

21. Embryonic Stem Cells and Cloning • Only fertilized egg cells and early cleavage cells are totipotent: • Ability to create the entire organism. • Reproductive cloning: • Adult stem cells can become totipotent if transplanted into egg cell cytoplasm. • Therapeutic cloning: • Nucleus transplantation to produce stem cells for purpose of growing specific tissue for the treatment of disease. • Pluripotent: • Cells obtained from inner cell mass of blastocyst (embryonic stem cells) can give rise to all tissues except the placenta. • Multipotent: • Can give rise to a number of differentiated cells. Department of Biochemistry, SJC, Trichy

22. hCG (Human Chorionic Gonadotropin) • Trophoblast cells secrete hCG: • Signals corpus luteum not to degenerate until placenta secretes adequate [hormones]. • Prevents immunological rejection of implanting embryo. • Has thyroid-stimulating ability. • Produces effects similar to LH. • Basis of pregnancy test. Insert fig. 20.46 Department of Biochemistry, SJC, Trichy

23. Placenta • Syncytiotrophoblast secretes enzymes that create blood filled cavities in the maternal tissue. • Cytotrophoblast then forms villi that grow into the pools of venous blood. • Produces chorion frondosum on the side that faces the uterine wall. • Other side of chorion bulges into the uterine cavity. Department of Biochemistry, SJC, Trichy

24. Formation of the Placenta and Amniotic Sac • Decidual reaction: • Endometrial growth. • Accumulation of glycogen. • Decidua basalis: • Maternal tissue in contact with the chorion frondosum. • Decidua basalis and chorion fondosum together become placenta. • Maternal and fetal blood do not mix. Insert fig. 20.50 Department of Biochemistry, SJC, Trichy

25. Amnion • Envelop the embryo and umbilical cord. • Amniotic fluid initially is isotonic, but as fetus develops; concentration changes by urine and sloughed cells of the fetus, placenta, and amniotic sac. Insert fig. 20.48 Department of Biochemistry, SJC, Trichy

26. Placenta Function • Site for exchange of gases and other molecules between maternal and fetal blood. • Gas exchange: • 02 and C02. • Nutrient exchange. • Waste exchange. • Synthesis of proteins,enzymes & Hormones. Department of Biochemistry, SJC, Trichy

27. Placental Hormones • hCS (chorionic somatomammotropin): • Actions similar to GH. • Actions similar to prolactin. • hCS and GH cause diabetic-like effect: • Lipolysis. • Polyuria. • Glucose sparing effects by maternal tissues. Ensure sufficient supply of glucose for placenta and fetus. Department of Biochemistry, SJC, Trichy

28. Placental Hormones (continued) • Fetal-placental unit: • Placenta must cooperate with the adrenal cortex in the fetus to produce estrogen. • Estrogen/estriol stimulates: • Endometrial growth. • Inhibition of prolactin secretion. • Growth of mammary ducts. • Enlargement of mother’s uterus. Department of Biochemistry, SJC, Trichy

29. Placental Hormones (continued) • Progesterone: • Suppresses uterine contractions. • Stimulates uterine growth. • Suppresses LH and FSH. • Stimulates development of alveolar tissue of the mammary gland. Department of Biochemistry, SJC, Trichy

30. Parturition • Estrogen in late pregnancy: • Stimulates production of oxytocin receptors in myometrium. • Produces receptors for prostaglandins. • Produces gap junctions between myometrium cells in uterus. • Factors responsible for initiation of labor are incompletely understood. Department of Biochemistry, SJC, Trichy

31. Parturition (continued) Department of Biochemistry, SJC, Trichy

32. Parturition (continued) • Fetal adrenal cortex: • Chain of events may be set in motion through CRH production. • Fetal adrenal zone secretes DHEAS, which travel from fetus and placenta. • Uterine contractions: • Oxytocin. • Prostaglandins. Department of Biochemistry, SJC, Trichy

33. Lactation • Hypothalamus releases PRH. • Anterior pituitary releases prolactin: • Stimulates milk production. • Prolactin secretion primarily controlled by PIH. • Oxytocin needed for “milk letdown.” Department of Biochemistry, SJC, Trichy

34. Lactation (continued) • Mammary gland: • Lobules contain glandular alveoli that secrete milk of the lactating female. • Alveoli secrete milk into secondary tubule that converge to form mammary duct. • Ampulla: • Where milk accumulates during nursing. • Neuroendocrine reflex: • Act of nursing maintains high levels of prolactin. • Sucking may cause release of PRH. Department of Biochemistry, SJC, Trichy

35. Milk-Ejection Reflex Department of Biochemistry, SJC, Trichy

36. REFERENCES • TEXT BOOK OF MEDICAL PHYSIOLOGY, ELEVENTH EDITION (2006), Arthur C. Guyton and John E. Hall. (Chapter -82). • HUMAN PHYSIOLOGY by Wikibooks contributors. • (http://en.wikibooks.org/wiki/Human_Physiology) • Devlin, 1997, TEXTBOOK OF BIOCHEMISTRY (WITH CLINICAL CORRELATION), John Wiley, USA. • Wilson and Foster, 1992, TEXTBOOK OF ENDOCRINOLOGY, (8thedn), W. B. Saunders, USA. Department of Biochemistry, SJC, Trichy