Antidopaminergic‐lnduced Hypothalamic LHRH Release and Pituitary Gonadotrophin Secretion in 12 Day‐Old Female and Male Rats

Abstract

In previous studies we have shown that the developing rat provides an interesting physiologic model in which the dopaminergic control of both LH and FSH is well defined in contrast to the controversial results obtained in adult rats. We wished to establish the role of testosterone in antidopaminergic induced gonadotrophins release in 12 day-old male and female rats, and evaluate the effect of antidopaminergic drugs at the hypothalamic level during this developmental stage. Haloperidol, an antidopaminergic drug, increased both LH and FSH in female 12 day-old rats but not in male littermates. The effect was blocked by bromocriptine and not by phentolamine indicating that haloperidol acted on the dopaminergic receptor, and that unspecific stimulation of the noradrenergic system was not involved. Haloperidol was ineffective when female rats were previously ovariectomized and injected with testosterone propionate at 9 days of age. If females were treated on the day of birth with testosterone propionate, haloperidol-induced FSH and LH release was also abolished. In control males haloperidol had no effect on the release of LH or FSH. But if males were orchidectomized at birth or at 9 days of age, haloperidol released both LH and FSH during the infantile period. In an attempt to establish the site of action of antidopaminergic drugs on gonadotrophin release, hypothalami (mediobasal and preoptic-suprachiasmatic area) from 12 day-old infant female rats were perifused with either haloperidol or domperidone (2*10(-6) M). Both drugs increased LHRH release into the perifusate. Besides haloperidol did not modify the release of LH or FSH from adenohypophyseal cells incubated in vitro. We therefore conclude that antidopaminergic-induced gonadotrophins release is modulated by serum testosterone concentrations, and that the site of action is probably the LHRH-secreting neuron of the hypothalamus.

Functional Characterisation of Eel Dopamine D2 Receptors and Involvement in the Direct Inhibition of Pituitary Gonadotrophins

“…In some teleosts species , as well as in various other vertebrates, such as amphibians , birds and mammals , in addition to the stimulatory effect of GnRH, dopamine (DA), a neurotransmitter of the central and peripheral nervous systems, has been identified as an inhibitory factor of reproductive function. This has been extensively studied in sheep, in which DA participates in the inhibition of gonadotrophic activity before puberty, as well as in the adult during seasonal anoestrus, by acting on GnRH neurones .…”

Dopaminergic inhibition of gonadotropin-releasing hormone neurons in the cichlid fish,Astatotilapia burtoni

“…However, the mechanisms underlying dopaminergic regulation of gonadotropic hormone release remain unclear, particularly in fish. Previous studies demonstrate that in tetrapods, dopamine inhibits GnRH1 release (Ching and Lin, 1994;Lacau-Mengido et al, 1993;Owens et al, 1980;Tasaka et al, 1985) via actions at both the hypothalamic soma of GnRH1 neurons and their synaptic terminals within the portal vasculature (Contijoch et al, 1992;Corio et al, 1990;Kuljis and Advis, 1989;Lehman et al, 1988;Pehrson et al, 1983;Ugrumov et al, 1989). In fish, dopamine was thought to act primarily within the pituitary, reducing gonadotropin release either indirectly, by suppressing GnRH1-releasing axons, or directly, by inhibiting pituitary gonadotropes (Levavi-Sivan et al, 1995;Vacher et al, 2002;Van Goor et al, 1998;Yu and Peter, 1992;Yu et al, 1991).…”

Access to the CNS: Biomarker Strategies for Dopaminergic Treatments

“…Similarly, LH and FSH were reduced after long-term chlorpromazine and fluphenazine treatment ( 166 , 170 ), while there was no effect observed after long-term sulpiride, risperidone and haloperidol treatment ( 167 , 168 ). After short-term haloperidol treatment, however, increased levels of LH and FSH were observed ( 162 ). Interestingly, the effect of short-term D 2 receptor antagonist treatment was observed in female but not in male rats ( 24 , 162 ).…”

“…After short-term haloperidol treatment, however, increased levels of LH and FSH were observed ( 162 ). Interestingly, the effect of short-term D 2 receptor antagonist treatment was observed in female but not in male rats ( 24 , 162 ).…”