Androgen treatment decreases estrogen receptor binding in the ventromedial nucleus of the rat brain: a quantitative in vitro autoradiographic analysis.
Androgens oppose the actions of estrogen on a number of neuroendocrine functions in the rat including prolactin and gonadotropin secretion and the activation of the female pattern of sex behavior. Although in nonneural tissues antiestrogenic actions of androgens have been related to actions at the level of the estrogen receptor, previous attempts to demonstrate effects of nonaromatizable androgens on estrogen receptor levels in the brain have been unsuccessful, possibly because of the poor anatomical resolution of the methods used. We have used a new in vitro autoradiographic assay combined with an 125I-labeled estrogen receptor ligand to test the hypothesis that the nonaromatizable androgen, 5 alpha-dihydrotestosterone (5 alpha-DHT), may act to reduce estrogen binding in specific regions of the brain involved in reproductive neuroendocrine and behavioral responses. This in vitro autoradiographic method allows selective measurement of occupied estrogen receptors in tissue sections. Gonadectomized/adrenalectomized rats were divided into two groups per sex. All animals received daily injections of estradiol benzoate (EB: 40 micrograms/kg body wt) for 4 days. Animals in the 5 alpha-DHT treatment group received 5 alpha-DHT (10 mg/kg body wt) every 12 h for 4 days, while animals in the control group received vehicle injections. Animals were killed 4 h after the final EB/5 alpha-DHT injection and their brains processed for in vitro autoradiography. As previously reported, higher levels of estrogen binding were observed in the ventrolateral aspect of the ventromedial nucleus (vIVMN) and the periventricular and medial preoptic area of the female compared to the male.(ABSTRACT TRUNCATED AT 250 WORDS)
Brown
T J
TJ
Division of Reproductive Science, Toronto Hospital Research Institute, Ontario, Canada.
Adler
G H
GH
Sharma
M
M
Hochberg
R B
RB
MacLusky
N J
NJ
D000315:Adrenalectomy; D000818:Animals; D001345:Autoradiography; D002369:Castration; D002552:Cerebral Ventricles / Q000378:metabolism; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011301:Preoptic Area / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D012727:Sex Characteristics; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*
D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D005485:Flutamide