Neurotransmitters involved in mediating the steroid-dependent suppression of pulsatile luteinizing hormone secretion in anestrous ewes: effects of receptor antagonists.
Seasonal anestrus in the ewe results from two effects of inhibitory photoperiods: a steroid-dependent effect by which estradiol gains the capacity to suppress LH pulse frequency and a steroid-independent effect that decreases LH pulse frequency in ovariectomized ewes. We have previously proposed that these effects of anestrous photoperiods result from the activation of inhibitory neuronal mechanisms at this time of year. In the present study, we used specific receptor antagonists to test this hypothesis and identify the neurotransmitters involved. Initially, eight 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. In contrast, neither pimozide nor phenoxybenzamine increased pulsatile LH secretion in midluteal phase ewes during the breeding season. These drugs did, however, produce other biological responses at this time of year; pimozide increased serum PRL 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 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.
Meyer
S L
SL
Goodman
R L
RL
D000780:Anestrus; D000818:Animals; D001947:Breeding; D002395:Catecholamines / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004971:Estrus; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000502:physiology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011247:Pregnancy; D012756:Sheep
D002395:Catecholamines; D012739:Gonadal Steroid Hormones; D018377:Neurotransmitter Agents; D010643:Phenoxybenzamine; D010868:Pimozide; D004958:Estradiol; D007986:Luteinizing Hormone