Gonadotropin-Releasing Hormone II Stimulates Female Sexual Behavior in Marmoset Monkeys

Abstract

GnRH II (pGlu-His-Trp-Ser-Try-Gly-Leu-Arg-Pro-GlyNH2), an evolutionarily conserved member of the GnRH family, stimulates reproductive behavior in a number of vertebrates. To explore a role for GnRH II in regulating primate sexual behavior, eight adult female common marmosets, each fitted with an indwelling intracerebroventricular (icv) cannula, were ovariectomized, implanted subcutaneously with empty (n = 4) or estradiol-filled (n = 4) SILASTIC brand capsules, and pair housed with an adult male mate. After icv infusion of vehicle or peptides, females were placed in an observation cage for 90 min, out of visual contact with other marmosets, before the 30-min behavioral test with their male partner. Compared with vehicle, GnRH II (1 and 10 microg) increased the total number of proceptive (sexual solicitation) behaviors (tongue flicking, proceptive stares, and frozen postures) exhibited by females toward their pair mates and specifically increased the frequency of freeze postures. Effects were maximal at 1 microg and not dependent upon estradiol supplementation. GnRH II agonists/GnRH I antagonists 135-18 (1 microg) and 132-25 (1 microg), which stimulate inositol phosphate production via the marmoset type II receptor, increased the frequency of total proceptive behavior but did not specifically stimulate freeze-posture behavior. In contrast, GnRH I, at 1 mug, did not alter the frequency of proceptive behaviors. Female receptivity (female compliance with male sexual behavior) was not altered by any of the peptides tested. These findings implicate a role for GnRH II and the cognate GnRH type II receptor in stimulating female marmoset sexual behavior.

Female reproductive activity and its endocrine correlates in the African lesser bushbaby, Galago moholi

“…Environmental cues, such as food availability, temperature and constant social stimuli have all been attributed to the initiation of oestrus (Perret 1986;Savini et al 2008) and might play a role for initiating oestrus in G. moholi as well. In our study, the fEM increase seen in conjunction with female reproductive activity seems to play an important role in initiating not only physical changes (vaginal opening), but also respective behavioural alterations (mating acceptance) and presumably female receptivity, as seen in various primate species such as common marmosets (Callithrix jacchus, Barnett et al 2006 moholi reproductive activity (Lipschitz 1997). Interestingly, only females displaying ovarian cyclicity successfully conceived in our study.…”

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

“…The antagonist 135-18 at 1 μg icv was able to Significantly stimulate proceptive behavior in the female marmoset in the absence of estrogen but was ineffective in the presence of estrogen. Another antagonist 135-25 which has similar agonistic properties to 135-18 at the type II GnRH receptor [8] was also able to stimulate proceptive behaviors in the female marmosets at a dose of 1 μg in the absence of estrogen replacement. In contrast, GnRH I at a dose of 1 μg was ineffective at stimulating proceptive reproductive behaviors.…”

“…Effect of icv administration of GnRH I, GnRH II and GnRH antagonist 135-18 on proceptive behaviors in female marmosets. GnRH II and antagonist 135-18 were Significantly different from vehicle control (Data derived from [8]). A proposed model of the role of GnRH II neurons in mediating reproductive behaviors in female mammals.…”

“…Studies on the effect of GnRH II on proceptive female behavior in ovariectomised and estrogen replaced female marmosets [8] indicated that intracerebral infusion of GnRH II at 1 and 10 μg doses stimulated proceptive behaviors in the absence of estrogen replacement (Fig. 12).…”

“…Since antiproliferative and apoptotic effects are mediated by different signaling pathways from those stimulating gonadotropins, we have undertaken a SAR study on the inhibition of cell number by GnRH analogs using a model system of HEK 293 cells expressing either the rat or the human GnRH receptor. Since GnRH II is more potent than GnRH I, the three different amino acids in GnRH II (His 5 , Trp 7 and Tyr 8) were systematically incorporated into synthetic GnRH I peptides and the relative antiproliferative and inositol phosphate production (G αq) compared. Tyr 5 substitution by His 5 resulted in increased affinity, which correlated with higher potencies for both of the responses studied.…”