Female Reproductive Endocrinology Kenneth L Campbell Professor of

Female Reproductive Endocrinology Kenneth L. Campbell Professor of Biology University of Massachusetts at Boston

What are endocrine systems for? Endocrine Functions • Maintain Internal Homeostasis • • Support Cell Growth Coordinate Development Coordinate Reproduction Facilitate Responses to External Stimuli

What are feedback systems? Feedbacks Generate Control Loops Negative + -- These maintain hormonal balance & are linked to homeostatic processes. If the multiplicative effect of the links in a control loop is negative, the entire control loop is negative. Positive + + These cause physiologic changes in the system. If the multiplicative effect of the links in a control loop is positive, the entire control loop is positive.

How dynamic are these systems? Hormone, receptor, transducer & effector levels vary with time. Some change over short terms, others over long terms. Levels also vary with developmental stage, gender, & health status.

How dynamic are these systems? After a 248. e. akamai. net/. . . /pubs/mmanual_home/ illus/i 232_1. gif

How dynamic are these systems?

How dynamic are these systems? www. antiaging. com/images/ testosterone_decline. gif

Outline of Female Reproduction 1. Adult anatomy 2. Embryogenesis 3. Sex determination 4. Hormonal controls 5. Puberty 6. Ovarian anatomy 7. Meiosis 8. Oogenesis 9. Contraception 10. Aging

Adult Female Anatomy

Female Embryogenesis

Female Germ Cell Migration www. med. unc. edu/embryo_images/unitgenital/genital_gifs/genital 008 -1. gif www. med. unc. edu/embryo_images/unitgenital/genital_gifs/genital 008 -2 all. gif

Female Germ Cell Migration

Sex Determination: Genetic

Sex Determination: Gonadal

Sex Determination: Gonadal www. med. unc. edu/embryo_images/unitgenital/genital_gifs/genital 010 -1. gif

Sex Determination: Internal Reproductive Tract

Sex Determination: External Reproductive Tract

Pituitary- Hypothalamic Associations www. cushings-help. com/ anterior-pituitary. gif

How are the gonads controlled? LH

How are the gonads controlled? FSH

Inhibin europe. obgyn. net/nederland/mp/ov ergang/images/overgang 14 x. gif

Steroid Synthesis arbl. cvmbs. colostate. edu/hbooks/pathphys/ endocrine/basics/ster oidogenesis. gif

Maturation: Hormonal

Testosterone in saliva in children & serum SHBG in adolescents & adults. The pubertal decrease in SHBG is less pronounced in women. www. biomedcentral. com/content/ figures/1471 -2431 -2 -5 -3 -l. jpg

Maturation: Tanner Stages www. cuhk. edu. hk/proj/growthstd/i mages/bpuberty. gif www. cuhk. edu. hk/proj/growthstd/imag es/gpuberty. gif

Maturation: Tanner Stages a 248. e. akamai. net/7/248/430/20020531071032/www. merck. c om/pubs/mmanual_home/illus/i 258

Meiosis: Males & Females Male Female

Oocyte Populations

Regressing Corpus Luteum Ovarian Anatomy Preovulatory Follicle www. vet. ksu. edu/media/images/t herio/ov-structures/02. jpg anatomy. med. unsw. edu. au/c bl/embryo/Notes/images/we ek 1/ovary. gif www. aksonogram. co m/images/ovary. jpg sufw. com. au/assets/imag es/gallery/normal%20 ovar y%20 with%20 follicle. jpg

Ovarian Anatomy Developing Follicles Ovarian Anatomy Corpus Luteum Rat antral follicle, courtesy P. Bagavandoss.

Hormonal Cycles: LH, FSH, Estradiol, Progesterone, Inhibin A & B europe. obgyn. net/nederland/mp/o vergang/images/overgang 14 x. gif After a 248. e. akamai. net/. . . /pubs/mmanual_home/ illus/i 232_1. gif

Folliculogenesis www. ohiorepromed. com/imag es/normal_ovulation_detail. jpg

Ovulation www. nfpsoftware. co m/ovul. gif medweb. uni-muenster. de/ institute/gyn/forschung/projekte/ovulation. jpg www. womenhealth. dsmu. ed u. ua/infoline/ovulation. gif

Granulosa Cell Metamorphosis & Corpus Luteum Formation

Coordinated Changes in: Uterus, Oviducts, & Cervix Endometrium: Follicular/Proliferative Phase Endometrium: Luteal/Secretory Phase Vaginal Lining

Fertilization

Female Contraceptive Use Tubal ligation: 27. 7% US, 39% Developing Surgery, injected occlusives Hormones: 31. 2% US, 15% Developing Steroids (OCs, injectables, implants) LHRH antagonists Barriers: 3. 6% US, 0. 3% Developing Diaphragms, cervical caps Foams, gels, creams, sponges IUDs: 0. 8% US, 26% Developing Medicated, unmedicated Withdrawal/Traditional: 3. 0% US, Periodic Abstinence 2. 3% US, Vasectomy/Condoms 31. 3% US, 9% Developing -- Developing 12% Developing 1995 US data: L Piccino, W Mosher, Fam Plann Perspect 30: 4 -10, 46 (1998); 1993 Developing world data: J Bongaarts, E Johnson, Stud Fam Plan 32: 24 (2002).

Female Aging, Menopause, HRT FSH (IU/L) [Ranges may vary among labs. ] ·<1 -3 prepubertal · 1 -8 males · 1 -11 females; follicular and luteal phase · 6 -26 at ovulation · 30 -118 post-menopausal www. familydoctor. co. uk/htdocs/MEN OPAUSE/MENOPAUSE 03. jpg press 2. nci. nih. gov/scie ncebehind/estrogen/ima ges/estrogen 22. gif

Raloxifene, Tamoxifen (SERMs) www. md. ucl. ac. be/entites/mint/intr/hainaut/dossierprojet/dossier docsem/menopause/i 15. gif [Belgian Menopause Society]

Low Fertility in Gainj vs Other Groups

How is prolactin controlled?

Courtesy of J Wood & D Holman.

Gainj Female Fertility Constraints

Early pregnancy loss is common

Acknowledgements Support from: NSF, Umass/Boston, Sandia National Labs, Hybritech, Quidel, Monoclonal Antibodies Inc. Gainj Project Turkana Project Related Studies The Gainj People Rees Midgley Al Hermalin Lora Myers Jim Wood Pat Johnson Ila Maslar Diana Lai Sam Refetoff Peter Smouse Peter Heywood Michael Alpers Brian Davison Yan Ren Lynne Shinto Diane Drinkwater Darryl Holman Bettina Shell All Turkana Subjects Mike Little Paul Leslie Ben Campbell Dhanesh Dookhran Kathy Whiteman Alexandra Evindar William Lukas Sandra Gray Jeanine Quigley Christine Sekadde -Kigondu Leah Kirumbi Kathy O’Connor Coralie Munro Susannah Barsom Ellie Brindle Cheryl Stroud Kai Orton Jodiann Thompson Yefim Proshchitskiy Yelena Filipova Matt Lopresti Oliver Schultheiss Cheryl Frederick Steve Monfort Malcolm Potts David Mc. Clelland (dec) (*in the lab at UMB)