1. BIO 351 Endocrinology, Medgar Evers College April 3, 2006 Male Reproductive Endocrinology Kenneth L. Campbell Prof. of Biology; Assoc. Dean of Science & Mathematics University of Massachusetts at Boston

2. This presentation is made possible by a grant entitled “Shortcourses in Endocrinology at Minority Undergraduate Institutions” from the National Institute of General Medical Sciences (NIGMS) to The Minority Affairs Committee of the Endocrine Society

3. Are You Interested In: Going away for the summer in 2007 to do research for 8 weeks in a cutting-edge endocrine lab in an area of your choice with a caring mentor? Receiving a two-year free membership in The Endocrine Society with many benefits, e.g., information about travel grants, scholarships, online journals, etc.? http://www.endo-society.org/minorityactivities/summer_research.cfm SUMMER RESEARCH OPPORTUNITIES FOR MINORITY STUDENTS

4. http://www.endo-society.org/minorityactivities/summer_research.cfm How do I qualify and What should I do? You can apply if you are: A full-time minority student beyond your sophomore year or if you are currently enrolled at a minority institution, and A U.S. citizen or permanent resident. For more details on eligibility and requirements, visit The Endocrine Society website at SUMMER RESEARCH OPPORTUNITIES FOR MINORITY STUDENTS

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

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

7. 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. www.antiaging.com/images/ testosterone_decline.gif After a248.e.akamai.net/.../pubs/mmanual_home/ illus/i232_1.gif

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

9. Adult Male Anatomy

10. Male Embryogenesis

11. Male Germ Cell Migration www.med.unc.edu/embryo_images/unit- genital/genital_gifs/genital008-1.gif www.med.unc.edu/embryo_images/unit- genital/genital_gifs/genital008-2all.gif

13. Sex Determination: Genetic

14. Sex Determination: Gonadal www.med.unc.edu/embryo_images/un it-genital/genital_gifs/genital010-1.gif

15. Sex Determination: Internal Reproductive Tract

16. Sex Determination: External Reproductive Tract

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

18. How are the gonads controlled? LH © Kenneth L. Campbell, 1997. All rights reserved.

19. How are the gonads controlled? FSH © Kenneth L. Campbell, 1997. All rights reserved.

20. Inhibin europe.obgyn.net/nederland/mp/o vergang/images/overgang14x.gif Female Males lack inhibin A. Inhibin B is inversely correlated with FSH & spermatogenesis in normal adults.

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

22. Maturation: Hormonal

23. Leydig Cell Populations Lejeune, H, R Habert, JM Saez, Origin, proliferation and differentiation of Leydig cells, J Mol Endocrinol 20:1-25, 1998.

24. Maturation: Tanner Stages www.cuhk.edu.hk/proj/growth std/images/bpuberty.gif www.cuhk.edu.hk/proj/growthstd/ images/gpuberty.gif a248.e.akamai.net/7/248/430/20020531071032/www. merck.com/pubs/mmanual_home/illus/i258

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

26. Testicular Anatomy trc.ucdavis.edu/mjguinan/apc100 /modules/Reproductive/mammal/ images/testis10.jpg

27. Meiosis: Males & Females MaleFemale

28. Spermatogenesis

29. Sperm Maturation Spermatozoa reach final shape in the testis, but they gain functional maturity while passing through the epididymus & female reproductive tract: activation of full motility, capacitation, in the vagina & cervix; final fertilizing ability after the acrosome reaction, usually near the egg.

30. Fertilization

31. Male Contraception Barriers condoms Vasectomy Hormones peripheral androgens +/- LHRH antagonists or agonists

32. Male Serum Hormone Age Profiles www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html Male Aging & Reproductive Senescence

33. www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html The ratio T/SHBG is the FAI, a Measure of free T. Adrenal androgens like DHEAS also decline with age.

34. Low Fertility in Gainj vs Other Groups

35. How is prolactin controlled?

37. FSH in Gainj Men

38. LH in Gainj Men

39. Many Gainj Men are Infertile

40. Support from: NSF, Umass/Boston, Sandia National Labs, Hybritech, Quidel, Monoclonal Antibodies Inc.Acknowledgements Gainj Project 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 Related Studies 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 McClelland (dec) Turkana Project 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 (*in the lab at UMB)

41. www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html Male Hormone Levels with Age