Does the hypothalamic tyrosine-hydroxylase inhibition mediate the positive feedback of progesterone on gonadotropin release in women?
Neuropharmacological studies suggest a common inhibitory role for the hypothalamic dopaminergic pathway on gonadotropin and prolactin pituitary release, in humans. As a consequence, it has been hypothesized that the inhibition of hypothalamic tyrosine-hydroxylase and the subsequent fall in dopamine synthesis is involved in the positive feedback of progesterone on LH and PRL pituitary release in estrogen-primed hypogonadal women. The aim of our study was to verify whether an inhibition of tyrosine-hydroxylase may really account for the progesterone action on gonadotropin and prolactin secretion. For this purpose, we compared the effect of a specific tyrosine-hydroxylase inhibitor (alpha-methyl-p-tyrosine, AMPT) with the effect of progesterone on gonadotropin and prolactin release in estrogen-primed postmenopausal women. Progesterone induced a marked release of LH (delta: 129.7 +/- 16.5 mlU/ml, mean +/- SE) and a slight increase in FSH (delta: 39.4 +/- 11.6 mlU/ml) and PRL (delta: 15.3 +/- 2.8 ng/ml) serum levels. Acute or two-day administration of AMPT was followed by a marked rise in PRL serum levels (delta: 82.9 +/- 13.8 and 88.3 +/- 8.2 ng/ml, respectively) while there were no significant increases in serum LH (delta: 5.4 +/- 2.6 and 3.3 +/- 4.6 mlU/ml) and FSH (delta: 3.4 +/- 0.9 and -0.4 +/- 2.9) concentrations. The ineffectiveness of a specific tyrosine-hydroxylase inhibitor in simulating the progesterone effect on gonadotropin secretion seems to negate the hypothesis that a reduction in hypothalamic dopaminergic activity mediates the positive feedback of progesterone on gonadotropin release.
D000368:Aged; D005246:Feedback; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000201:enzymology*; D007986:Luteinizing Hormone / Q000097:blood; D008781:Methyltyrosines / Q000494:pharmacology; D008875:Middle Aged; D011374:Progesterone / Q000502:physiology*; D011388:Prolactin / Q000097:blood; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D019805:alpha-Methyltyrosine
D006065:Gonadotropins, Pituitary; D008781:Methyltyrosines; D011374:Progesterone; D019805:alpha-Methyltyrosine; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D014446:Tyrosine 3-Monooxygenase