Does the Hypothalamic Tyrosine-Hydroxylase Inhibition Mediate the Positive Feedback of Progesterone on Gonadotropin Release in Women?

Summary

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 estrogenprimed 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 (α-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 (Δ: 129.7 ± 16.5 mlU/ml, mean ± SE) and a slight increase in FSH (Δ: 39.4 ± 11.6mlU/ml) and PRL (Δ: 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 (Δ: 82.9 ± 13.8 and 88.3 ± 8.2 ng/ml, respectively) while there were no significant increases in serum LH (Δ: 5.4 ± 2.6 and 3.3 ± 4.6 mlU/ml) and FSH (Δ: 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.

Key-Words:

α-Methyl-p-Tyrosine - Dopamine - Gonadotropins - Prolactin - Tyrosine-Hydroxylase Inhibition - Progesterone Positive Feedback