The long-range goal of this work is to clarify the functional organization of neural circuitry underling reproductive physiology and behavior. Central to this goal is a better understanding of the organization of forebrain neural circuitry involved in these functions and the role that gonadal steroids play in their development and regulation. The proposed experiments represent a logical extension of past work and are a necessary first step toward identifying the cellular events involved in the modulation of specific neural systems by hormonal feedback. These experiments are designed to examine the hypothesis that circulating gonadal steroid hormones regulate tyrosine hydroxylase (THE) and/or proenkephalin (ENK) mRNA levels within two sexually dimorphic populations of cells in the anteroventral periventricular nucleus (AVPv). The AVPv appears to be a nodal point in the neural control of ovulation, and projects to the arcuate nucleus of the hypothalamus, a nucleus that is widely regarded to play an important role in gonadotropin secretion. Retrograde and anterograde axonal transport techniques will be used in combination with immunohistochemistry to determine whether THE and/or ENK are contained within this pathway. The influence of gonadectomy and various sex steroid treatments on The and ENK expression will be assessed in male and female rats at the level of single cells by using in situ hybridization histochemistry to detect possible changes in mRNA levels. The results of these experiments will gain added physiological relevance by comparing them with those obtained in normally cycling female rats at each stage of the estrous cycle. Finally, surgically lesioned animals will be studied with in situ hybridization in order to examine the possibility that any direct effects of gonadal steroids on THE and ENK expression may be augmented by neural influences from other steroid sensitive regions that project to the AVPv. The results of the proposed experiments should greatly contribute to what is currently known regarding the molecular mechanisms by which gonadal hormones control the neural events mediating ovulation. Knowledge of these mechanisms is essential to our emerging understanding of the processes that underlie infertility and fertility control.
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