Effect of Histamine and Histamine Blockers on the Ovulatory Process in the in Vitro Perfused Rabbit Ovary

Abstract

An increase in the content of histamine in the ovary following luteinizing hormone (LH) release and the inhibition of ovulation in the rabbit by antihistamines suggest that histamine may be involved in the ovulatory process. The effects of various doses of histamine and antihistamines on ovulation were investigated using the in vitro perfused rabbit ovary system. Histamine (100 ng/ml) added to the perfusate at hourly intervals induced ovulation, although at a rate below that observed following human chorionic gonadotropin (hCG) administration. Cimetidine (10 micrograms/ml), an H2 blocker, inhibited histamine-induced ovulation, while the H1 blocker, chlorpheniramine (66.7 micrograms/ml), failed to do so. Neither cimetidine nor chlorpheniramine was able to block ovulation following hCG (50 IU). In all experimental groups in which histamine was used to induce ovulation, both extruded ova and follicular oocytes remained in an immature stage and displayed little evidence of degeneration. In contrast, a high percentage of ova exposed to hCG were mature. Ovarian edema was increased in ovaries in which ovulation occurred, regardless of treatment. A linear correlation was noted between ovulatory efficiency and degree of ovarian edema. Histamine may be an intermediary in the mechanism of follicular rupture, but does not support ovum maturation. However, the inability of H1 and H2 antagonists to block hCG-induced ovulation raises questions regarding the role of histamine in the physiologic process of ovulation.

Histamine induces ovulation in the isolated perfused rat ovary

“…This agrees with the incidence found by Kobayashi et al (1983), who also reported that follicle growth and rupture differed in rabbit ovaries exposed to histamine or LH: a characteristic apex or stigma was not present, and the oocytes often remained in an immature stage. Moreover, the action of histamine in the present study did not require an intact prostaglandin synthesis system, whereas indomethacin blocks the gonadotrophin-stimulated follicular rupture (Armstrong, 1981).…”

“…However, this antagonist, like chlorpheniramine, lowered the number of ovulations induced with histamine in the isolated perfused rabbit ovary (Kobayashi et al, 1983). The present experiments on rat ovaries agree with reports from studies on rabbits suggesting that the histamine-induced ovulation involves both receptor subtypes (Wallach et al, 1978;Kobayashi et al, 1983).…”

“…However, this antagonist, like chlorpheniramine, lowered the number of ovulations induced with histamine in the isolated perfused rabbit ovary (Kobayashi et al, 1983). The present experiments on rat ovaries agree with reports from studies on rabbits suggesting that the histamine-induced ovulation involves both receptor subtypes (Wallach et al, 1978;Kobayashi et al, 1983). The H2-receptor antagonism in our experiments was achieved with two kinds of selective antagonists of different chemical nature, cimetidine (Brogden, Heel, Speight & Avery, 1978) and ranitidine (Brogden, Carmine, Heel, Speight & Avery, 1982).…”

“…The H2-receptor antagonist, cimetidine, appears to be unable to affect the hCG-induced ovulatory response of rabbits in vitro (Kobayashi et al, 1983) or in vivo (Espey et al, 1982). However, this antagonist, like chlorpheniramine, lowered the number of ovulations induced with histamine in the isolated perfused rabbit ovary (Kobayashi et al, 1983).…”

Roxatidine, an H2Receptor Blocker, is an Estrogenic Compound—Experimental Evidence

“…Histamine is involved in the various stages of reproduction including ovulation [Szego and Gitin 1964;Schmidt et al 1988;Kobayashi et al 1983;Jaiswal and Krishna 1994;Schmidt et al 1987;Halterman and Murdoch 1986;Kitai et al 1985], implantation [Liu et al 2004;Zhao et al 2000;Paria et al 1998;2002;Oikawa et al 2003;Hoos and Hoffman 1983], and decidualization [Shelesnyak 1960;Zipper et al 1965]. Various researchers have demonstrated that H 2 receptor blockers possess anti-fertility activity [Agrawal and Alvin Jose 2009;Agrawal and Aravinda 1995;Brandon and Wallis 1977].…”