Alpha-adrenergic regulation of androgen receptor concentration in the preoptic area of the rat.
We examined the effect of the pharmacological disruption of the catecholaminergic system on the concentration of nuclear androgen receptor, as measured by the in vitro binding of methyltrienolone ([3H]R1881) to salt extracts of anterior pituitary (AP), preoptic area (POA) and medial basal hypothalamus (MBH). Treatment of gonadectomized male and female rats with the dopamine-beta-hydroxylase inhibitor, diethyldithiocarbamate (400 mg/kg b. wt.), 30 min before treatment with dihydrotestosterone (1 mg/animal) produced a decrease in the number of nuclear androgen receptor compared with saline-treated controls (P less than 0.05). This effect was specific for the POA and was not present 15 h after DHT treatment. There was no effect on cytosolic androgen receptor nor was there a drug effect on the apparent dissociation constant (Kd) of [3H]R1881 binding to hypothalamus-preoptic area cytosols. Treatment of intact males and castrated, testosterone-treated males with the alpha 1- and alpha 2-adrenergic antagonists, prazosin (5 mg/kg b. wt.) and yohimbine (2 mg/kg b. wt.), respectively, resulted in a significant decrease in the number of nuclear AR 2 h following drug treatment (P less than 0.05). There was no effect of the beta-adrenergic receptor antagonist propranolol (10 mg/kg b. wt.) when given to intact animals, nor was there an effect of idazoxan (5 mg/kg) when given to testosterone-treated animals. The effects of yohimbine and prazosin were restricted to the POA. None of the drugs competed with the binding of [3H]R1881 for the androgen receptor nor did they alter the Kd of cytosol or nuclear androgen receptor. These data provide evidence for an adrenergic interaction with the POA androgen receptor and suggest a role for catecholamines in modulating androgen sensitivity in the rat brain.
Handa
R J
RJ
Department of Physiology, Oregon Health Sciences University, Portland 97201.
Resko
J A
JA
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002369:Castration; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology; D005260:Female; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011301:Preoptic Area / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011944:Receptors, Androgen; D015016:Yohimbine; D004050:Ditiocarb; D011224:Prazosin