The role of hypothalamic adrenergic receptors in preventing testosterone-induced androgenization in the female rat brain.
Androgenization of the female neonatal rat brain by testosterone and the subsequent development of persistent estrus in the adult can be blocked by drugs which interfere with normal hypothalamic neuronal function. The mechanism of action of these drugs was studied. A 25-micrograms dose of testosterone propionate at 5 days of age produced a 69% incidence of persistent estrus at 90 days of age. alpha-Methyl-p-tyrosine given with testosterone propionate resulted in an 81% incidence of persistent estrus. Therefore, hypothalamic norepinephrine depletion did not prevent androgenization. Tyramine (100 micrograms) inhibited androgenization to an incidence of 27% by 90 days. Phenoxybenzamine (50 micrograms) and phentolamine (50 micrograms) each reduced the incidence to 0%. Combining the beta-antagonist propranolol with phenoxybenzamine or phentolamine reversed the block in androgenization, resulting in 37% and 50% incidences of persistent estrus, respectively. Tyramine causes the release of neuronal stores of norepinephrine which is turn stimulates alpha- and beta-adrenergic receptors. The action of tyramine implicates adrenergic stimulation as a mechanism for the inhibition of androgenization, but does not define which receptor type is involved. In addition to postsynaptic alpha-blockade, phenoxybenzamine and phentolamine can cause presynaptic alpha-blockade, resulting in increased neuronal norepinephrine release and beta-stimulation. When the beta-antagonist propranolol was added to the alpha-antagonists, the block in androgenization was reversed. Therefore, we conclude that beta-adrenergic receptor stimulation prevents androgenization of the neonatal rat brain.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D013739:Testosterone; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine; D014439:Tyramine; D010646:Phentolamine