Evaluation of a Possible Role for the Dopamine D₁ and D₂ Receptors in the Steroid‐Dependent Suppression of Luteinizing Hormone Secretion in the Seasonally Anoestrous Ewe

Abstract

This study was undertaken to determine whether dopaminergic suppression of pulsatile luteinizing hormone (LH) secretion during seasonal anoestrus in the ewe is mediated via the dopamine D, or D, receptor. This was tested by 1) assessing the response to dopamine D, and D, antagonists during seasonal anoestrus, and 2) determining the ability of D, and D, agonists to suppress pulsatile LH secretion during the breeding season. In seasonally anoestrous ewes the D, antagonist pirnozide increased LH pulse frequency although this effect did not reach significance (P=0.07). The D, antagonist SCH 23390 had no effect on LH pulse frequency. LH pulse amplitude and mean LH were not affected by either treatment. During the breeding season, ovariectomized oestradiol-implanted ewes were injected intracerebroventricularly with vehicle, LY 171555 (dopamine D, agonist) and SKF 38393 (D, agonist) with each drug tested at 50pg and 200pg. At the higher dose, LY 171555 significantly (P<O.O5) reduced LH pulse frequency in the 2 h period immediately after treatment. Mean LH declined at both doses but only in the first hour after treatment.SKF 38393 did not affect LH pulse frequency, pulse amplitude or mean LH. These results suggest that the D, receptor is not involved in the suppression of pulsatile LH secretion during seasonal anoestrus. Dopaminergic suppression of pulsatile LH secretion is mediated via the D, receptor but the significance of this neurotransmitter in the seasonal suppression of LH remains to be elucidated.During seasonal anoestrus in the ewe, luteinizing hormone (LH) :;ulse frequency is low ( I , 2) and, as a consequence, ovarian dlicles d o not complete development to the preovulatory stage : :). The low LH pulse frequency during seasonal anoestrus is iue, at least in part, to an increase in sensitivity of the hypothal-:.mic gonadotrophin-releasing hormone pulse generator to oestrac8iol negative feedback (4). The site where oestradiol exerts this (.tlect has not been determined but as there are no oestradiol I kaptors within the gonadotrophin-releasing hormone neurons (.!) it appears that an intermediary is involved. Potential candida I cs are the hypothalamic dopaminergic pathways which synapse M ith gonadotrophin-releasing hormone neurons (6, 7) and contain wtradiol receptors (8). Dopamine is known to inhibit LH sicretion in the ewe (9) and further, the dopamine D, receptor 11 11 lagonist pimozide increases LH pulse frequency in seasonally awestrous ovary intact ewes, providing evidence for increased dcipaminergic tone at this time (10). The corollary of this argument 1s that dopamine should be capable of suppressing the LH pulse Wlerator. This is difficult to demonstrate during seasonal anoestrus because LH pulse frequency is already so low that even -with extremely long sampling periods it is difficult to obtain a reliable estimate of pulse frequency and therefore almost impossible to demonstrate an inhibitory treatment effect. However, in ovariectomized ewes in which LH pulse frequency is high, Meyer and G...

Plasma prolactin changes in anoestrous ewes after infusion of genistein into the third ventricle

“…Indeed, the suppression of prolactin concentrations following infusion of D2-like (quinpirole) agonist into MBH (Anderson et al, 1997) supports findings of Wolinska et al (1977) and Curlewis et al (1991). Dopamine might also act through dopamine D2 receptors located on lactotrophs in the anterior pituitary in the ewe (Anderson et al, 1997;Bertrand et al, 1999).…”

Implication of D2-like dopaminergic receptors in the median eminence during the establishment of long-day inhibition of LH secretion in the ewe

“…Intracerebroventricular administration of quinpirole reduced LH pulse frequency in OVX+E ewes during the breeding season, whereas the same treatment with SKF38393 did not have any effect on LH secretion (Curlewis et al 1991). Conversely, i.v.…”

“…Conversely, i.v. injection of pimozide tends to increase LH pulse frequency in OVX+E ewes during anestrus, while SCH23390 has no effect (Curlewis et al 1991). Moreover, placement of pimozide microimplants in the ME in anestrous ewes stimulated LH secretion (Havern et al 1991), whereas local injection of quinpirole in the ME-arcuate nucleus region inhibited LH secretion in OVX ewes (Anderson et al 1997).…”

“…The action of dopamine can be mediated by two major types of dopaminergic receptors, D1-like and D2-like (Kebabian & Calne 1979). Although the implication of D2-like receptors in the control of LH secretion has been shown in several physiological conditions in sheep (Meyer & Goodman 1985, Curlewis et al 1991, Havern et al 1991, Anderson et al 1997, the nature of the receptors involved in the ME is not known. Indeed, effects on LH secretion of D2-like receptor analogs delivered in the ME were observed, but dose-dependent comparisons of the effects of specific analogs of each type of receptor have not been performed in this site.…”

Pulsatile Luteinizing Hormone Secretion in the Ovariectomized, Thyroidectomized Red Deer Hind Following Treatment with Dopaminergic and Opioidergic Agonists and Antagonists1

“…Since bromocriptine suppressed LH concentration and pulse frequency only under short days, and sulpiride increased LH concentration and pulse frequency only under long days, it was concluded in that study, as in most similar studies using ovariectomized estradiol-treated ewes [18,51,52] or intact ewes [18,53,54], that an inhibitory dopaminergic neural system is activated during the nonbreeding season to suppress LH and bring about the sexually inactive state. In two studies using ovariectomized estradiol-treated ewes [55,56] and one using intact or testosterone-treated castrated rams [56], TC # 331 there was no LH response to the dopamine antagonist pimozide.…”