Ethanol inhibits luteinizing hormone-releasing hormone (LHRH) secretion by blocking the response of LHRH neuronal terminals to nitric oxide.

Abstract

It has previously been shown that alcohol can suppress reproduction in humans, monkeys, and small rodents by inhibiting release of luteinizing hormone (LH). The principal action is via suppression of the release of LH-releasing hormone (LHRH) both in vivo and in vitro. The present experiments were designed to determine the mechanism by which alcohol inhibits LHRH release. Previous research has indicated that the release of LHRH is controlled by nitric oxide (NO). The Alcohol suppresses reproductive function in humans, monkeys, and small rodents, such as the rat (1-4). In the rat,The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. 3416 chronic administration of alcohol not only inhibits the estrous cycle but it can also delay onset of puberty (4, 5). In conscious animals, administration of alcohol via an indwelling gastric cannula in doses that produce mild intoxication inhibits pulsatile release of luteinizing hormone (LH), but not folliclestimulating hormone, within a few minutes (4). In this situation, the responsiveness of the pituitary gland to acute injection of LH-releasing hormone (LHRH) is unaffected, which shows that the mechanism of this effect is via suppression of the pulsatile LHRH release into the hypophyseal portal vessels that triggers release of LH from the gonadotropes of the adenohypophysis. The interference with estrous cycles and the delayed onset of puberty in the female rat is likely brought about by this suppression by ethanol of LHRH release (5). Secretion of LH is required to stimulate the ovary to produce ovarian steroids responsible for the estrous cycle, and the onset of puberty is consequently delayed.We have recently shown that nitric oxide (NO) controls the release of LHRH both in vivo and in vitro (6). On the basis of in vitro experiments employing incubation of medial basal hypothalamic (MBH) explants in a static incubation system, it has been determined that norepinephrine activates constitutive NO synthase (NOS) in neurons in this region (NOergic neurons) (6, 7). The NO released from these neurons diffuses to LHRH terminals, where it induces the release of LHRH, probably by activating cyclooxygenase 1. The activated cyclooxygenase then converts arachidonate into prostaglandin E2 (PGE2) (8). PGE2 activates adenylate cyclase, causing generation of cAMP, which acts via protein kinase A to evoke exocytosis of LHRH granules into the hypophyseal portal vessels for its delivery to the anterior pituitary gland (9, 10). The LHRH acts on the gonadotropes and causes a pulse of LH release. Support for this theoretical pathway stems from the ability of inhibitors of NOS, such as NG-monomethyl-Larginine, to inhibit LHRH release, whereas releasers of NO, such as sodium nitroprusside (NP), induce LHRH release both in vitro and in vivo (6-9).We have identified the site of inhibitory action of interleukin 1 (IL-1) on LHRH release...

Role of leptin in hypothalamic–pituitary function

“…Since, NPY inhibited LH release in intact and castrated male and ovariectomized female rats (29,30), we hypothesize that NPY decreases the release of LHRH by inhibiting the noradrenergic neurons that have been shown to mediate pulsatile release of LHRH (31,32). Therefore, when the release of NPY is inhibited by leptin, noradrenergic impulses are generated that act on ␣ 1 receptors on the NO-ergic neurons, causing the release of NO, which diffuses to the LHRH terminals and activates LHRH release by activating guanylate cyclase and cyclooxygenase 1 , as shown in our prior experiments (31,32). The LHRH enters the portal vessels and is carried to the anterior pituitary gland, where it acts to stimulate FSH and particularly LH release by combining with its receptors on the gonadotropes.…”

Role of the testis in the response of the pituitary-testicular axis to nitric oxide-related agents

“…The mechanisms proposed to explain the role of NO on the hypothalamic-pituitary-testicular axis involve effects at different levels (6). At the hypothalamic level, most studies have reported stimulatory effects (7)(8)(9), although inhibitory effects have been also reported (10). At the pituitary level, NO inhibits LH secretion (11).…”

Nitric oxide synthase‐cyclo‐oxygenase pathways in organum vasculosum laminae terminalis: possible role in pyrogenic fever in rabbits

“…In contrast, aminoguanidine is a 2 fold more potent inhibitor of iNOS from LPS-treated RAW 264.7 macrophages than L-NMMA (Misko etal., 1993), and L-NAME is a 3 fold less potent inhibitor of iNOS in the murine macrophage cell-line J774 compared to L-NMMA (McCall et at., 1991 (Ignarro 1984;Mayer et at., 1993) (Nakamori et at., 1994 (Mellion et al, 1981;Ignarro, 1991). This increase in cyclic GMP activates phospholipase A2 to provide arachidonic acid, the substrate for conversion by the activated COX to PGE2 (Canteros et al, 1995). Thus, the synergistic production of prostaglandins by NO and cyclic GMP may be involved in the pyrogenic effect of SNAP.…”