Biology 595EN Endocrinology

October 28, 2003

Male Reproductive Endocrinology

Kenneth L. Campbell

Professor of Biology

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

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 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.

--+

++

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/unit-genital/genital_gifs/genital008-1.gif

www.med.unc.edu/embryo_images/unit-genital/genital_gifs/genital008-2all.gif

Sex Determination: Genetic

Sex Determination: Gonadal

www.med.unc.edu/embryo_images/unit-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

europe.obgyn.net/nederland/mp/overgang/images/overgang14x.gif

Female

Males lack inhibin A. Inhibin B is inversely correlated with FSH & spermatogenesis

in normal adults.

SteroidSynthesis

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

www.cuhk.edu.hk/proj/growthstd/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

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.

Testicular Anatomy

trc.ucdavis.edu/mjguinan/apc100/modules/Reproductive/mammal/

images/testis10.jpg

Meiosis: Males & FemalesMale 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

Barrierscondoms

Vasectomy

Hormones peripheral androgens +/- LHRH antagonists or agonists

Male Serum HormoneAge Profiles

www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html

Male Aging & Reproductive Senescence

www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html

The ratio T/SHBGis the FAI, a

Measure of free T.

Adrenal androgenslike DHEAS alsodecline with age.

Low Fertility in Gainj vs Other Groups

How is prolactin controlled?

FSH in Gainj Men

LH in Gainj Men

Many Gainj Men are Infertile

Support from: NSF, Umass/Boston, Sandia National Labs, Hybritech, Quidel, Monoclonal Antibodies Inc.

AcknowledgementsAcknowledgements

Gainj ProjectThe Gainj PeopleRees MidgleyAl HermalinLora MyersJim WoodPat JohnsonIla Maslar Diana LaiSam Refetoff Peter SmousePeter HeywoodMichael AlpersBrian DavisonYan Ren Lynne ShintoDiane DrinkwaterDarryl HolmanBettina Shell

Related StudiesKathy O’ConnorCoralie MunroSusannah Barsom Ellie Brindle Cheryl StroudKai OrtonJodiann ThompsonYefim ProshchitskiyYelena FilipovaMatt LoprestiOliver SchultheissCheryl FrederickSteve MonfortMalcolm PottsDavid McClelland (dec)

Turkana ProjectAll Turkana SubjectsMike LittlePaul LeslieBen CampbellDhanesh DookhranKathy WhitemanAlexandra EvindarWilliam LukasSandra GrayJeanine QuigleyChristine Sekadde -KigonduLeah Kirumbi

(*in the lab at UMB)

www.dpcweb.com/documents/news&views/spring_02/the_aging_male.html

Male Hormone Levels with Age