Gonadotrophin‐releasing hormone (GnRH) is a hypothalamic decapeptide with an undisputed role as a primary regulator of gonadal function. It exerts this regulation by controlling the release of gonadotrophins. However, it is becoming apparent that GnRH may have a variety of other vital roles in normal physiology. A reconsideration of the potential widespread action that this traditional reproductive hormone exerts may lead to the generation of novel therapies and provide insight into seemingly incongruent outcomes from current treatments using GnRH analogues to combat diseases such as prostate cancer.

Gonadotropin Releasing Hormone-I (GnRH) has been implicated in an array of functions outside the neuroendocrine reproductive axis. Previous investigations have reported extensive GnRH binding in numerous sites and this has been supported by in situ hybridization studies reporting GnRH receptor mRNA distribution. The present study on mice and sheep supports and extends these earlier investigations by revealing the distribution of cells immunoreactive for the GnRH receptor. In addition to sites previously shown to express GnRH receptors such as the hippocampus, amygdala and the arcuate nucleus, the improved resolution afforded by immunocytochemistry detected cells in the mitral cell lay of the olfactory bulb as well as the central grey of the mesencephalon. In addition, GnRH receptor immunoreactive neurons in the hippocampus and mesencephalon of the sheep were shown to colocalize with estrogen receptor beta. Although GnRH may act at some of these sites to regulate reproductive processes, evidence is accumulating to support an extra-reproductive role for this hypothalamic decapeptide.

Increasing evidence suggests that multihormonal cells in the pituitary gland may be more commonplace than previously thought. This has forced us to reconsider our classical view of cell populations in the pituitary gland. Studies so far have focused almost exclusively on the rat, and there is a dearth of information on other species. Our first objective was to determine whether a subpopulation of gonadotropes also express somatotropin in the ewe, as reported in the rat. In addition, we sought to determine whether gonadotropes express any of the other known pituitary hormones. Finally, we investigated whether the stage of the estrous cycle influenced the occurrence of these pluripotential gonadotropes. We found that a small population of betaLH-immunoreactive cells also expresses immunoreactive GH, prolactin and TSH. No gonadotropes colocalized with ACTH. Significantly (P<0.001) more gonadotropes expressed GH during the luteal (10.7+/-0.4%) than the late follicular (5.4+/-0.3%) phase but there was no difference between the luteal and follicular phases in the proportion of gonadotropes expressing prolactin (follicular: 5.7+/-0.7%; luteal: 5.5+/-0.6%) or TSH (follicular: 3.1+/-0.7%; luteal: 4.2+/-0.5%). Similarly, there was a significant (P<0.05) difference in the proportion of GH-immunoreactive cells expressing betaLH immunoreactivity in the luteal (5.9+/-0.3%) and follicular (3.4+/-0.5%) phases but no difference in the proportion of prolactin- (follicular: 2.2+/-0.7%; luteal: 2.0+/-0.8%) or TSH-immunoreactive cells (follicular: 9.6+/-3.7%; luteal: 10.8+/-2.9%) expressing betaLH. The specific function of these multihormonal gonadotropes in sheep remains to be determined.