Progesterone modulation of androgen receptors in the brain and pituitary of male guinea pigs.
Androgen receptors (AR) were determined in cytosol and nuclear extracts of pituitary and neural tissue from intact male guinea pigs by a binding assay using [3H]dihydrotestosterone as ligand. Saturation analyses of cytosol from hypothalamus-preoptic area (POA)-amygdala regions and anterior pituitary revealed receptors (ARc) with apparent Kd values of 2.52 and 3.83 X 10(-10) M, respectively. Nuclear salt extracts from the same tissues contained receptors (ARn) with Kd values of 4.38 and 5.12 X 10(-10) M. Reproductive behavior of 10 males was observed with receptive females for 10 min once a week. After 4 weeks, half of the animals received 10 mg progesterone (P)/day for an additional 4 weeks. P treatment significantly (P less than 0.05) increased latency to first mount and decreased mounts per test period. After behavioral testing, analysis of the AR content of specific brain regions revealed that the highest concentrations of ARc and ARn were in the POA and medial basal hypothalamus, and the lowest were in the cerebral cortex. The ARn content was significantly suppressed in POA and medial basal hypothalamus (P less than 0.05) from P-treated males compared to the control value. These data show that AR content is highest in areas thought to control behavior and gonadotropin release within the brain of the male guinea pig. In addition, the antiandrogenic actions of P on the central nervous system, which in this experiment were expressed as a significant decline in reproductive behavior, may be explained by its interference with the retention of the AR in the nucleus.
Connolly
P B
PB
Department of Physiology, Oregon Health Sciences University, Portland 97201.
Handa
R J
RJ
Resko
J A
JA
D000679:Amygdala / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D006168:Guinea Pigs; D007031:Hypothalamus / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011301:Preoptic Area / Q000378:metabolism / Q000648:ultrastructure; D011374:Progesterone / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D012098:Reproduction / Q000187:drug effects; D012726:Sexual Behavior, Animal / Q000187:drug effects; D014018:Tissue Distribution
D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D011374:Progesterone