Enhancement of the luteinising hormone surge by male olfactory signals is associated with anteroventral periventricular Kiss1 cell activation in female rats

Abstract

Olfactory stimuli play an important role in regulating reproductive functions in mammals. The present study investigated the effect of olfactory signals derived from male rats on kisspeptin neuronal activity and luteinising hormone (LH) secretion in female rats. Wistar-Imamichi strain female rats were ovariectomised (OVX) and implanted with preovulatory levels of 17β-oestradiol (E ). OVX+E rats were killed 1 hour after exposure to either: clean bedding, female-soiled bedding or male-soiled bedding. Dual staining for Kiss1 mRNA in situ hybridisation and c-Fos immunohistochemistry revealed that the numbers of Kiss1-expressing cells and c-Fos-immunopositive Kiss1-expressing cells in the anteroventral periventricular nucleus (AVPV) were significantly higher in OVX+E rats exposed to male-soiled bedding than those of the other groups. No significant difference was found with respect to the number of c-Fos-immunopositive Kiss1-expressing cells in the arcuate nucleus and c-Fos-immunopositive Gnrh1-expressing cells between the groups. The number of c-Fos-immunopositive cells was also significantly higher in the limbic system consisting of several nuclei, such as the bed nucleus of the stria terminalis, the cortical amygdala and the medial amygdala, in OVX+E rats exposed to male-soiled bedding than the other groups. OVX+E rats exposed to male-soiled bedding showed apparent LH surges, and the peak of the LH surge and area under the curve of LH concentrations in the OVX+E group were significantly higher than those of the other two groups. These results suggest that olfactory signals derived from male rats activate AVPV kisspeptin neurones, likely via the limbic system, resulting in enhancement of the peak of the LH surge in female rats. Taken together, the results of the present study suggests that AVPV kisspeptin neurones are a target of olfactory signals to modulate LH release in female rats.

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

“…Consistent with this, a recent study in female rats (ovariectomised and implanted with preovulatory oestradiol levels) demonstrated increased AVPV and limbic (but not ARC) kisspeptin neuronal Fos expression following exposure to male-soiled bedding [33]. Furthermore, these female rats showed enhanced LH surges compared to female rats exposed to clean or female-soiled bedding, therefore providing functional relevance [33].…”

“…Moreover, an even greater increase in RP3V kisspeptin neuronal Fos expression was observed in female wild-type mice exposed to male urinary odours (compared to female oestrous urine or control water) [32]. Consistent with this, a recent study in female rats (ovariectomised and implanted with preovulatory oestradiol levels) demonstrated increased AVPV and limbic (but not ARC) kisspeptin neuronal Fos expression following exposure to male-soiled bedding [33]. Furthermore, these female rats showed enhanced LH surges compared to female rats exposed to clean or female-soiled bedding, therefore providing functional relevance [33].…”

“…1). Kisspeptin signalling is required for male olfactory partner preference [30], is enhanced by opposite-sex urinary odours [32,33], modulates mate preference [31], enhances auditory-reproductive behaviour [34], dampens fear responses [36], modulates anxiety [31,36,42], has antidepressant-like effects [40,44], and triggers erections [51]. Furthermore, in healthy heterosexual men, kisspeptin enhances limbic and paralimbic brain activity specifically in response to visual-evoked sexual and romantic stimuli and these enhancements correlate with behavioural measures including sexual aversion, reward, and mood [40].…”

“…This included the anterior and posterior cingulate, amygdala, thalamus, and globus pallidus, which are all implicated in romantic, maternal, and unconditional love [53][54][55][56] and consistent with structures known to be involved in kisspeptin signalling in humans [19,20] and rodents [10,15,21,23,24]. Interestingly, kisspeptins enhanced activation of the amygdala in response to bonding images correlated with improved positive mood [40], a Sexual behaviours -Enhances limbic and paralimbic brain activity with correlations to reward, sexual aversion, and positive mood (H) [40] -Triggers erections (R) [51] Fear -Reduces fear responses (Z) [36][37][38]43] Social behaviours -MeA kisspeptin neurone apposition with dopaminergic and vasopressinergic neurones (R) [24] Audition -Male rodent ultrasonic vocalisations increase female ARC kisspeptin activity which correlates to the duration of female searching for male (R) [34] Mood -Antidepressant-like effects (R, H) [40,44] -Anxiolytic effects (R, Z) [31,36] -Anxiogenic effects (R) [42] Olfaction -Kisspeptin anatomical framework (R, H) [24] -Kiss1r and MeA Kiss1 roles in male olfactory partner preference (R) [30,31] -Opposite-sex urinary odours stimulate RP3V and limbic kisspeptin neurones and enhance LH surge (R) [32,33] Kisspeptin signalling potential mechanism that may contribute to the desire to bond with a partner.…”

Medial Amygdala <b><i>Kiss1</i></b> Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

“…However, the neuronal and molecular basis of processing pheromone signals appears to be sexually dimorphic. In female rats, male odours lead to activation of AVPV Kiss neurons coincident with elevated LH and increased sexual behaviour [41]. Similarly, in mice, male urine leads to the activation of AVPV Kiss neurons and increased lordosis behaviour in females [42].…”