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 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 SUMMER RESEARCH OPPORTUNITIES FOR MINORITY STUDENTS 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 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 http://www.endo-society.org/minorityactivities/summer_research.cfm What are endocrine systems for? Endocrine Functions • Maintain Internal Homeostasis • • • • Support Cell Growth Coordinate Development Coordinate Reproduction Facilitate Responses to External Stimuli Feedbacks Generate Control Loops Negative + -- These maintain hormonal balance & are often linked What are feedback systems? 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. 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 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 Adult Male Anatomy Male Embryogenesis Male Germ Cell Migration www.med.unc.edu/embryo_images/unitgenital/genital_gifs/genital008-1.gif www.med.unc.edu/embryo_images/unitgenital/genital_gifs/genital008-2all.gif Sex Determination: Genetic Sex Determination: Gonadal www.med.unc.edu/embryo_images/un it-genital/genital_gifs/genital010-1.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 © Kenneth L. Campbell, 1997. All rights reserved. How are the gonads controlled? FSH © Kenneth L. Campbell, 1997. All rights reserved. Inhibin Female Males lack inhibin A. Inhibin B is inversely correlated with FSH & spermatogenesis in normal adults. europe.obgyn.net/nederland/mp/o vergang/images/overgang14x.gif Steroid Synthesis arbl.cvmbs.colostate. edu/hbooks/pathphys/ endocrine/basics/ster oidogenesis.gif Maturation: Hormonal Leydig Cell Populations Lejeune, H, R Habert, JM Saez, Origin, proliferation and differentiation of Leydig cells, J Mol Endocrinol 20:1-25, 1998. Maturation: Tanner Stages a248.e.akamai.net/7/248/430/20020531071032/www. www.cuhk.edu.hk/proj/growth www.cuhk.edu.hk/proj/growthstd/ merck.com/pubs/mmanual_home/illus/i258 std/images/bpuberty.gif images/gpuberty.gif 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 Testicular Anatomy trc.ucdavis.edu/mjguinan/apc100 /modules/Reproductive/mammal/ images/testis10.jpg Meiosis: Males & Females Male Female Spermatogenesis 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. Fertilization Male Contraception Barriers condoms Vasectomy Hormones peripheral androgens +/- LHRH antagonists or agonists MaleMale Serum Hormone Aging & Age Profiles Reproductive Senescence 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. www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html Low Fertility in Gainj vs Other Groups How is prolactin controlled? FSH in Gainj Men LH in Gainj Men Many Gainj Men are Infertile Acknowledgements Support from: NSF, Umass/Boston, Sandia National Labs, Hybritech, Quidel, Monoclonal Antibodies Inc. Gainj Project Turkana 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 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) 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) Male Hormone Levels with Age www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html