Neurotransmitters Involved in Mediating the Steroid-Dependent Suppression of Pulsatile Luteinizing Hormone Secretion in Anestrous Ewes: Effects of Receptor Antagonists*

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Abstract
Seasonal anestrus in the ewe results from 2 effects of inhibitory photoperiods: a steroid-dependent effect, by which estradiol gains the capacity to suppress LH [luteinizing hormone] pulse frequency, and a steroid-independent effect that decreases LH pulse frequency in ovariectomized ewes. Apparently, these effects of anestrous photoperiods result from the activation of inhibitory neuronal mechanisms at this time of year. Specific receptor antagonists were used to test this hypothesis and to identify the neurotransmitters involved. Initally, 8 receptor antagonists were screened for their ability to increase pulsatile LH secretion in ovary-intact anestrous ewes. Of these, only pimozide, a dopaminergic antagonist, and phenoxybenzamine, an .alpha.-adrenergic antagonist, increased LH pulse frequency. Neither pimozide nor phenoxybenzamine increased pulsatile LH secretion in midluteal phase ewes during the breeding season. These drugs did produce other biological responses at this time of year: pimozide increased serum PRL [prolactin] levels, and phenoxybenzamine decreased arterial blood pressure. Pimozide also increased pulsatile LH secretion in ovariectomized ewes treated with estradiol in anestrus to suppress LH pulse frequency, but phenoxybenzamine was ineffective in these animals. Neither drug increased LH in ovariectomized ewes not treated with estradiol. The seasonal variation in the ability of pimozide and phenoxybenzamine to increase LH secretion in ovary-intact ewes supports the hypothesis that inhibitory neural mechanisms suppressing GnRH [gonadotropin releasing hormone] are activated during anestrus, and suggests that dopaminergic and/or .alpha.-adrenergic neurons are involved. In addition, the steroid-dependent effect of anestrous photoperiods may be exerted through the ability of estradiol to stimulate inhibitory dopaminergic neurons which are only active at this time of year.

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