Norepinephrine stimulates testosterone aromatization and inhibits 5 alpha reduction via beta-adrenoceptors in rat pineal gland.
The possible modulatory role of the sympathetic nervous system on testosterone aromatization and 5 alpha reduction by rat pineal gland was examined in vitro. NE (10 microM) added to pineal organ cultures increased by 72% the conversion of [14C]testosterone into estradiol and depressed by 39 and 53% that into the 5 alpha-reduced metabolites 5 alpha-dihydrotestosterone (5-DHT) and 5 alpha-androstanediol (5 alpha-diol). Both effects of NE were negated by the addition of the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Dibutyryl cAMP (0.1 mM) mimicked the effect of NE on pineal [14C]testosterone metabolism; it also mimicked the NE-induced inhibition of [14C]progesterone reduction to 5 alpha-pregnanedione and 3 alpha-hydroxy-5 alpha-pregnan-20-one by rat pineal gland explants. At the end of the dark phase of the daily photoperiod, pineal aromatization of testosterone was significantly higher, and 5 alpha reduction lower, than in rats killed at noon. Pineal glands obtained from rats subjected to superior cervical ganglionectomy 12 h earlier exhibited increased conversion of [14C]testosterone into estradiol, and depressed synthesis of 5 alpha-reduced metabolites, as compared with their respective sham-operated controls. 3 days after ganglionectomy a diminished testosterone aromatization was found. These results suggest that the increased release of NE from pineal sympathetic nerve endings stimulates testosterone aromatization and inhibits 5 alpha reduction via a beta-adrenoceptor.
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002940:Circadian Rhythm; D005728:Ganglia, Sympathetic / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013739:Testosterone / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D013739:Testosterone; D003994:Bucladesine; D011433:Propranolol; D010088:Oxidoreductases; D001141:Aromatase; D009638:Norepinephrine; D010646:Phentolamine