Neuroendocrinology, Hormone-Neurotransmitter Interactions, Hormones and Behavior, Reproductive Endocrinology, Peripubertal Stress and Reproduction

In order to learn how hormones act in the brain to modify brain function and behavior and how the social environment can influences these processes, we study the cellular and neuroanatomical mechanisms of ovarian steroid hormone action on reproductive behavior and the interactions between neurotransmitters and steroid hormone receptors.

We study the cellular processes by which steroid hormones act in neurons, particularly with respect to their involvement in reproductive behavior. During the estrous cycle of female rats and other rodent species, the ovarian hormones, estradiol and progesterone, regulate the expression of reproductive behaviors. The sensitivity of specific neurons to each of the hormones is determined in part by the concentrations of hormone-specific intracellular receptors. Intracellular steroid hormone receptors are essential in mediating the effects of steroid hormones on some behaviors, possibly by modulating gene transcription and synthesis of specific proteins.

It has been widely held that in order for steroid receptors to be activated, hormone must be available to bind to the receptors. However, in collaboration with others, we have shown that neurotransmitters can activate steroid hormone receptors without hormone. Furthermore, we have shown that mating stimulation by a male rat can activate the female's neural steroid hormone receptors. This activation in turn causes neuronal changes, which result in changes in behavior and physiology. These hormone-independent changes resemble those induced by hormone-dependent activation of the receptors. In other words, the male's behavior toward the female, which alters neurotransmitters in her brain, does many of the same things that the hormones secreted from her ovaries can. This provides a model for the regulation of hormonally regulated processes by environmental stimulation, including but not limited to, social stimulation.

A new interest of our group is the study of the long-term effects of exposure to particular stressors around the time of puberty. We have recently discovered that exposure to particular stressors (shipping; a bacterial endotoxin), but not others, only in the peripubertal period causes enduring changes in response to ovarian steroid hormones (i.e., defeminization of response to estradiol and progesterone) in adulthood months later. Similarly, we have observed changes in levels of steroid hormone receptors in particular neuroanatomical areas in adulthood in response to these peripubertal treatments. Our current work focuses on the mechanisms by which these particular stressors cause enduring changes in an animal's response to sex steroid hormones. We also are trying to determine how wide-spread this phenomenon is. That is, what behavioral and physiological end-points, besides reproductive behavior, are influenced by this stress exposure.

We use a variety of biochemical and anatomical techniques including immunocytochemistry, in situ hybridization, tract-tracing in conjunction with steroid hormone receptor immunocytochemistry, electron microscopy, steroid hormone receptor binding assays, intracranial application of neuroactive substances, radioimmunoassay, and behavioral observation. In many experiments, we study hormonal processes at the level of individual neurons as well at the behavioral level.

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