1. Aging of the Male Reproductive System Spring 2007 PS Timiras

2. Dr. Brown Sequard (Physiologist, Univ. Sorbonne, Paris) introduced the idea that some glands secrete internally (in the blood) potent substances that affect the whole organism. In 1905, these substances were called “hormones” by the British physiologist E.H. Starling.

4. Anatomy of the Male Reproductive Tract TESTIS Primary sex organ suspended outside of the body in the scrotum Secondary male sex organs include: EPIDIDYMIS, VAS DEFERENS, EJACULATORY DUCTS which carry sperm to the urethra SEMINAL VESISCLES, PROSTATE, & BULBOURETHRAL GLANDS which secrete seminal fluid PENIS with URETHRA through which flow both urine and semen In humans the principal reproductive organ is the brain In addition to the brain, the male reproductive system consists of the:

5. A simplified version of the male reproductive endocrinology: The hypothalamus releases GnRH into the circulatory system and, through blood, directly into the pituitary. GnRH triggers the release of the pituitary LH and FSH that stimulate the testes to testosterone secretion and sperm production.

6. the GERM CELLS or GAMETES, involved in fertilization. the INTERSTITIAL CELLS of LEYDIG that secrete testosterone, the major androgen the SERTOLI CELLS with secretory and reproductive functions The testis, the male primary reproductive organ, contains three types of cells, all necessary for reproduction:

8. With Age: On the average, the male reproductive function remains normal (or only slightly diminished in some individuals) until advanced old age (80+ years) when it decreases Subtle changes include: GnRH Sensitivity of androgen secretion to LH Sensitivity of negative feedback between GnRH and LH

9. Figure 12.2 Differences in levels (total, bioavailable, and percentage) of free/bioavailable testosterone Young Old

10. Serum LH concentration With aging, loss of high- amplitude LH pulses despite normal or increased pituitary LH stores Serum testosterone concentration With aging, decreased responsiveness of testis androgen secretion to LH YoungOlder

11. TABLE 12-2 SELECTED NEUROENDOCRINE MODELING ISSUES IN THE AGING MALE REPRODUCTIVE AXIS 1. How does the timing of GnRH pulse-generator change with age? 2. Which alterations in the aging male reproductive axis reflect pathophysiology versus secondary adaptations? 3. What mechanisms account for greater inter-subject heterogeneity in aging of GnRH-LH testosterone secretion?

12. Aging of the Prostate

13. Figure 19.7

14. Table 19-12 The Prostate and Testosterone The healthy prostate is dependent on androgens for growth In the prostate: testosterone  dihydrotestosterone (DHT) The enzyme catalyzing this reaction is 5-  -reductase DHT stimulates growth of the prostate

15. Table 19-13 Normal Aging of the Prostate After age 40: Outer regions: Atrophy of smooth muscle and proliferation of connective tissue Flattening of secretory epithelium Inner region: Increase in the number of cells present (hyperplasia) After age 60: Slower, but more uniform atrophy of the prostate Accumulation of prostate concretions

16. Figure 19.8

19. Treatment of Prostate Cancer Depends on Life expectancy Overall health status Personal preferences Size of the prostate State of disease Treatments include: Watchful waiting Surgery Radiation Therapy Hormonal Therapy Cryotherapy **PSA controversy pp. 353, 354**