Differential Effects of an Luteinizing-Hormone-Releasing Hormone (LHRH) Antagonist Analogue on Lordosis Behavior Induced by LHRH and the LHRH Fragment Ac-LHRH^5–1⁰

Abstract

Both the luteinizing-hormone-releasing hormone (LHRH) decapeptide and an LHRH fragment consisting of the last 6 amino acids of the decapeptide, Ac-LHRH^5–10, have been shown to enhance lordosis behavior in ovariectomized, estradiol-benzoate treated female rats. Although the behavioral efficacy of the 2 peptides is similar, several lines of research suggest that the fragment and the decapeptide may act via different mechanisms. The present study attempted to differentiate the behavioral action of the 2 peptides by administering a long-acting LHRH antagonist analogue prior to infusion of either Ac-LHRH^5–10 or LHRH. Without antagonist administration, the decapeptide and the fragment were equally effective in elevating lordotic posturing 90 min after bilateral infusion through cannulae positioned in the ventromedial nucleus of the hypothalamus (VMH). Infusion of a potent LHRH antagonist analogue [Ac-dehydro, Pro¹, pCl, D-Phe², DTrp^3,6]-LHRH, into the VMH significantly reduced the lordosis-to-mount ratio in animals subsequently treated with the LHRH decapeptide, but had no significant effect on lordotic behavior when the animals were subsequently infused with the Ac-LHRH^5–10 fragment. The results indicate that LHRH enhancement of mating behavior is a receptor-mediated event and suggest that the Ac-LHRH^5–10 fragment enhances lordotic behavior via a mechanism that is distinct from that of the LHRH decapeptide.

Hormonal and neurotransmitter regulation of GnRH gene expression and related reproductive behaviors

“…There is evidence that only a fragment of the GnRH molecule is required for facilitation of lordosis, and degradation of the decapeptide may be an important physiological step in the coordination of receptivity and ovulation (Dudley et al, 1983;Moss, 1988, 1991;Moss and Dudley, 1990). This concept is supported by the finding that GnRH effects on behavior can be pharmacologically separated from those mediating LH release, as shown by selective GnRH analogues that do not induce ovulation but do facilitate lordosis (Zadina et aL, 1981;Sakuma and Pfaff, 1983).…”

“…This concept is supported by the finding that GnRH effects on behavior can be pharmacologically separated from those mediating LH release, as shown by selective GnRH analogues that do not induce ovulation but do facilitate lordosis (Zadina et aL, 1981;Sakuma and Pfaff, 1983). In addition, distinct mechanisms of action may exist such that the full decapeptide works by way of a receptormediated event, whereas its active C-terminal fragment acts independently (Moss and Dudley, 1990).…”

Preferential Distribution of C-Terminal Fragments of [Hydroxyproline⁹]LHRH in the Rat Hippocampus and Olfactory Bulb

“…These effects, in particular induction of mating behavior, appear to depend primarily upon the C-terminal sequence of LHRH; only C-, not Nfragments were found active [14,15], In view of their pro duction in extrahypothalamic structures and of their high er stability towards degradating enzymes, [Hyp9]LHRH derived C-fragments could well represent the endogenous active molecules responsible for those effects. Their ac tion may be mediated by receptors distinct of those of LHRH itself [3][4][5], as suggested by their differential bind ing potency on membrane homogenates prepared from the brain or the pituitary [4], inasmuch as mating behav ior induced by C-fragments of LHRH is not abolished by conventional antagonists of LHRH receptors [17].…”

“…Interestingly, C-terminal fragments of LHRH were found as effective as LHRH itself on these responses [14][15][16]. These effects could thus be mediated by a distinct subtype of the LHRH receptor recognizing shorter pep tides, inasmuch as behavioral effects of LHRH fragments are not all prevented by LHRH antagonists [17], In a pre vious study, we characterized [hydroxyproline9]LHRFI ([Hyp9]LHRH) [ 18] as an alternate endogenous posttranslational product of the LHRH precursor [ 19]. Both in vivo and in vitro, [Hyp9]LHRH is able to stimulate release of LH and FSH [20] as well as that of placental hCG [21 ].…”

Estradiol-Dependency of Sexual Behavior Manifestation at the Post-LH Surge Period in Ovariectomized Goat.

“…Actually, the central or systemic administration of GnRH was shown to potentiate the lordosis response (rodents' receptive behavior) in ovariectomized rats [22][23][24][25][26][27][28][29] and in hypogonadal mice [30] primed with estrogen in doses that were too low to initiate lordosis. Moreover, treatments with anti-GnRH globulins [28,29,31] or GnRH antagonists [26,31] disrupted lordosis response in estrogen-primed ovariectomized rats. The effect of GnRH could not be ascribed to LH or folliclestimulating hormone release, since the lordosis was facilitated by the injection of GnRH in estrogenprimed ovariectomized rats, which had been hypophysectomized [32].…”