Neonatal RU-486 (mifepristone) exposure increases androgen receptor immunoreactivity and sexual behavior in male rats.
Progesterone and progestin receptors (PRs) are known to play a role in the development of brain physiology and behavior in many different species. The distribution and regulation of PRs within the developing brain suggest that they likely contribute to the organization of the brain and behavior in a sex-specific manner. We examined the role of PR signaling during development on the organization of adult sexual behavior and androgen receptor (AR) expression in the brain. We administered the PR antagonist, RU-486, subcutaneously to male and female rats on postnatal days 1-7 (0=day of birth) and examined adult sexual behavior and AR-immunoreactivity (AR-ir) in the adult brain. A typical sex difference in lordosis quotient (LQ) was observed and neonatal RU-486 treatment did not alter this behavior. In contrast, neonatal RU-486 treatment increased adult male sexual behavior and AR-ir in several brain areas in males. These data indicate that a transient disruption in PR signaling during development can have lasting consequences on the male brain and may increase male sexual behavior in part by increasing AR expression, and therefore androgen sensitivity, in adulthood.
Department of Psychology, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: forbeslorman@wisc.edu.
Robin
R
Forbes-Lorman
Department of Psychology, University of Wisconsin-Madison, Madison, WI 53706, USA; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Anthony P
AP
Auger
Department of Psychology, University of Wisconsin-Madison, Madison, WI 53706, USA; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Catherine J
CJ
Auger
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology
D006727:Hormone Antagonists; D011944:Receptors, Androgen; D015735:Mifepristone
AR; Androgen receptors; BSTMP; ER; LQ; LSV; MeA; PN; PR; Pir; Progesterone; Progestin receptors; RU-486; Sexual behavior; TBS; VMHdm; androgen receptor; dorsomedial ventromedial hypothalamus; estrogen receptor; immunoreactive; ir; lordosis quotient; mPOA; medial amygdala; medial posterior division of the bed nucleus of the stria terminalis; medial preoptic area; piriform cortex; postnatal day; progestin receptor; tris-buffered saline; ventral lateral septum