Effects of female pheromones on gonadotropin-releasing hormone gene expression and luteinizing hormone release in male wild-type and oestrogen receptor-alpha knockout mice

Pheromones are an important class of environmental cues that affect the hyp othalamic-pituitary-gonadal axis in a variety of vertebrate species, includ ing humans. When male mice contact female-soiled bedding, or urine, they di splay a reflexive luteinizing hormone (LH) surge within 30 min, Aside from the requirement that males have gonads to show this response, the physiolog ical mechanisms that underlie this pituitary response are unknown. In this experiment, we asked if female pheromones acted at the level of gonadotropi n-releasing hormone (GnRH) gene expression to affect this hormone response. In addition, we also examined the contribution of one of the oestrogen rec eptors (ER alpha) by studying this neuroendocrine reflex in wild-type and o estrogen receptor-cc knockout (ER alpha KO) males. Both ER alpha KO and wil d-type males showed the expected LH surge, 45 and 90 min after contact with female pheromones. Males housed in clean bedding or bedding soiled by anot her adult male did not display the LH elevation. Interestingly, this dramat ic change in LH concentrations was not accompanied by any alterations in Gn RH mRNA expression or levels of primary transcript in the preoptic area-ant erior hypothalamus. The one exception to this was a significant increase in GnRH mRNA expression in tissue collected from wild-type males exposed to b edding from another male. This is particularly intriguing since LH was not elevated in these males. These data replicate and extend our previous findi ng that ER alpha KO males do exhibit an LH surge in response to female pher omones. Thus, this neuroendocrine response is regulated by a steroid recept or other than ER alpha and does not require alterations in GnRH mRNA expres sion.