Inhibition Of Gonadotropin-releasing Hormone Research Articles

Dopaminergic mechanisms and luteinizing hormone secretion. I. Acute administration of the dopamine agonist bromocriptine does not inhibit luteinizing hormone release in hyperprolactinemic women.

The concept that domapinergic mechanisms control LH secretion by modulation of gonadotropin-releasing hormone (GnRH) has been recently investigated in man. Since hyperprolactinemia is associated with increased hypothalamic dopamine turnover (which may reflect increased dopaminergic activity), inhibition of GnRH by dopamine in this situation would be maximal. Additional stimulation of dopamine receptors by a dopamine agonist would not be expected to result in further inhibition of LH release. Twelve hyperprolactinemic women were studied on 2 days during which measurements of serum PRL and LH were made over 11.5 h. Day 1 served as a control for day 2 when 2.5 mg of the dopamine agonist bromocriptine were administered orally at 0900 h. While serum PRL and LH levels on day 1 showed small fluctuations (+/- 10%), serum PRL on day 2 fell by 82%. Serum LH concentrations on day 2 remained unchanged. The demonstration or the efficacy of bromocriptine in lowering PRL levels documents the expected increase in dopaminergic tone; however, the lack of effect of bromocriptine in surpressing LH release suggests that either there is already maximal endogenous inhibition of GnRH in hyperprolactinemic women or, alternatively, that dopaminergic mechanisms are unimportant in the control of LH secretion.

Effect of an antagonistic analog of gonadotropin releasing hormone upon ovarian granulosa cell function

We have recently demonstrated that gonadotropin releasing hormone (GnRH) acts directly on ovarian granulosa cells to inhibit the follicle stimulating hormone (FSH)-induced increase in granulosa cell steroidogenesis in vitro . A GnRH antagonist, [D-pGlu 1, D-Phe 2, D-Trp 3,6] GnRH (A), which is known to antagonize GnRH-stimulated gonadotropin release by cultured pituitary cells, was tested in the granulosa cell system. GnRH (10 −8M) inhibited estrogen and progesterone production by FSH-treated granulosa cells in vitro , whereas the antagonist A (10 −6M) did not affect FSH stimulation of steroidogenesis. Antagonist A, when added together with GnRH and FSH, blocked the GnRH inhibition of FSH-induced steroidogenesis. Estrogen and progesterone production by granulosa cells was increased by 50% at a molar ratio (IDR 50) of 20 1 and 12 1 ([antagonist]/[GnRH]), respectively. At 10 −6M, antagonist A completely prevented the GnRH (10 −8M) inhibition. A similar effect of antagonist A was seen in FSH-induced increase of luteinizing hormone (LH) receptor content. FSH treatment for 2 days in vitro induced an 8-fold increase in LH receptor content in cultured granulosa cells; concomitant treatment with 10 −8M GnRH completely inhibited the FSH effect. Antagonist A (10 −6M), by itself, had no effect on the FSH action. However, when added together with FSH and GnRH, antagonist A completely abolished the inhibitory effect of GnRH. These results demonstrate that the direct inhibitory effect of GnRH on granulosa cell function can be prevented by a GnRH antagonist and that the GnRH action at the ovarian level may require stringent stereospecific interactions of these peptides with putative GnRH recognition sites.