Effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on responsiveness of the male rat reproductive system to testosterone stimulation in adulthood.
Previous studies strongly suggested that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may cause incomplete imprinting of the male reproductive system, i.e., that in utero and lactational exposure to TCDD may alter the responsiveness of sex organs to steroids in adulthood. To test this hypothesis, male rats born to dams dosed with 0.7 microgram TCDD/kg or vehicle on Gestation Day 15 were castrated at 63 days of age and implanted with graded lengths of Silastic capsule(s) containing crystalline testosterone. Resultant plasma testosterone concentrations ranged from castrate to about fourfold higher than physiological. Male reproductive organs which are imprinted by exposure to perinatal androgens and which are highly responsive to androgen stimulation in adulthood were assessed 3 weeks later. Ventral prostate weight and protein content in TCDD-exposed rats were significantly less responsive to testosterone regardless of the amount implanted. These decreases were not secondary to alterations in plasma or prostate testosterone or 5 alpha-dihydrotestosterone concentrations in adulthood, none of which was affected by TCDD. In contrast to its effects on ventral prostate weight and protein, TCDD had no effect on responsiveness to testosterone as measured by ventral prostate DNA content; seminal vesicle weight, protein content, or DNA content; penis weight; or plasma LH concentrations. We conclude that in utero and lactational TCDD exposure inhibits imprinting of ventral prostate weight and protein but does not result in a universal inhibition of imprinting. Androgen responsiveness of the prostate is uniquely sensitive to in utero and lactational TCDD exposure and provides a model to study the mechanism by which exposure to TCDD during fetal and early postnatal development modulates hormone-mediated responses in adulthood.
Bjerke
D L
DL
School of Pharmacy, University of Wisconsin, Madison 53706.
Sommer
R J
RJ
Moore
R W
RW
Peterson
R E
RE
D000375:Aging / Q000502:physiology; D000728:Androgens / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005260:Female; D005837:Genitalia, Male / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007774:Lactation; D008297:Male; D010413:Penis / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012669:Seminal Vesicles / Q000187:drug effects; D013268:Stimulation, Chemical; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000728:Androgens; D004343:Drug Implants; D000072317:Polychlorinated Dibenzodioxins; D013739:Testosterone