Involvement of H₁ Histamine Receptor in Basal and Estrogen-Stimulated Luteinizing Hormone-Releasing Hormone Secretion in Rats in vitro

Abstract

For determination of the roles of histamine and its receptors, H₁ and H₂, in the control of basal and estrogen-induced LH-RH secretion, the mediobasal hypothalamus (MBH) and/or pituitary was excised from normally cycling female rats and perifused in an in vitro sequential double chamber perifusion system. Administration of 10^–7M histamine caused significant release (90–170% increase, p < 0.05) of LH from the pituitary in sequence with the MBH, whereas 10^–7M histamine had no effect on LH release from the pituitary perifused alone; administration of 10^–5M 2-methylhistamine, an H₁ agonist, induced significant release (50–120% increase, p < 0.05) of LH-RH from the MBH, and addition of 10^–5M mepyramine, and H₁ antagonist, abolished this LH-RH release. The LH concentrations in the efflux were not affected by the administration of the H2 agonist 4-methylhistamine. Estradiol caused significant release of LH-RH from the MBH and LH from the pituitary in sequence with the MBH. The estradiol-induced release of LH-RH and LH were completely abolished by perifusion with medium containing 10^–5M mepyramine. The H₂ receptor antagonist ranitidine did not affect estradiol-induced LH release. Histamine did not change the LH release induced by 20 ng LH-RH. These findings suggest that histamine induces release of hypothalamic LH-RH, and that histamine H₁ receptors in the hypothalamus are involved in the basal and estradiol-induced LH-RH release.

Estrogen Receptor Immunoreactivity Is Present in the Majority of Central Histaminergic Neurons: Evidence for a New Neuroendocrine Pathway Associated with Luteinizing Hormone-Releasing Hormone-Synthesizing Neurons in Rats and Humans1

“…This notion is supported by recent evidence (9) showing that H1 receptors are expressed in GT-1 cells, a cell line derived from LHRH-producing neurons (31). Furthermore, it has been found that the stimulation by estrogen of LHRH release from the hypothalamus in vitro can be blocked by an H1 but not an H2 antagonist (24).…”

“…It was subsequently shown that this amine stimulates LHRH and LH secretion from an in vitro preparation containing the medial basal hypothalamus and pituitary of female rats (24); this stimulatory effect can also be achieved using an H1 but not an H2 agonist and can be blocked by an H1 antagonist (24). In contrast, in vitro studies on tissues taken from male rats have reported that histamine is without effect not only on LH release when the pituitary is perifused alone (24) but also on LHRH release from the mediobasal hypothalamus (25).…”

On the Possibility of Participation of Histamine Neurons in Suppression of Luteinizing Hormone Secretion by Fasting in Rats

“…On the other hand, stimulating effects of HA on the secretion of GnRH by the in vitro cultured hypothalamic tissues and GT cells have been well proved 20,24,25) and it was also revealed by in vivo experiments that ICV injection of HA increased the secretion of LH in proestrous and ovariectomized estrogen-and estrogen plus progesterone-treated rats4,6,18), although similar treatments caused the suppression of LH secretion in male rats5,6). HA, therefore, can be considered to be one of candidates of the transmitter which plays an important role in the regulation of LH secretion in relation to the feeding cycle and/or feeding manipulation.…”

Lack of effect of intracerebroventricular infusion of H1 or H2 histamine receptor antagonists on luteinizing hormone secretion in fed or fasted rats

“…Histaminergic postsynaptic events modulate both H1 and H2 receptors. The H1 receptor, but not the H2 receptor, has been implicated in the secretion of LH and of gonadotropin-releasing hormone (GnRH) in vitro (Miyake et al 1987;Otsuka et al 1989;Noris et al 1995). ICV infusion of HA was shown to increase LH secretion in rats in proestrus (Donoso 1978) as well as in ovariectomized (OVX), estradiol (E 2 )-primed (Libertun and McCann 1976) and OVX, E 2 -and progesteroneprimed (Donoso et al 1976) rats, with this effect being mediated by the H1 receptor (Fekete et al 1999).…”