Crews Laboratory: Focus of Research

Here I seek to (i) determine how stimuli relevant to reproduction are perceived and integrated in the central nervous system, (ii) demonstrate how the central nervous system regulates internal reproductive state, and (iii) examine how changes in internal state influence the expression of behavior (c.f., 85, 144, 209 and 225). Three animal model systems have been developed in the course of this research: the green anole lizard, the red-sided garter snake, and two species of whiptail lizards. This work has revealed that great diversity exists among vertebrates in reproductive behaviors and the neuroendocrine mechanisms underlying these behaviors. Comparisons of animals with different hormone-brain-behavior relationships suggest three factors which may explain species differences in endocrine physiology and behavior: (i) sensitivity to sex steroid hormones, (ii) hormone-dependent regulation of sex steroid hormone receptor gene expression, and (iii) neuroanatomical distribution of steroid receptor gene expression, especially in non-limbic structures.

This work with reptiles has led us to re-examine certain assumptions in behavioral neuroendocrinology. One relevation concerns the idea that progesterone is a "female-specific" hormone with no function in males. We have found, however, that progesterone is vital to the display of male copulatory behavior in lizards as well as in mice and rats and, further, that androgen and progesterone synergize in males much like estrogen and progesterone synergize in females to facilitate sexual receptivity (c.f., 189 and 199). To study further the role of the progesterone and its receptor in the regulation of male sexual behavior, we have shown that male mice lacking the progesterone receptor (knockouts) show deficits in their mating behavior and sensitivity to androgen treatment (e.g., 237). This led recently to studies of the role of dopamine, a neurotransmitter implicated in both male and female sexual behavior We find that the progesterone receptor can be activated by dopamine independently of its natural ligand progesterone. Further, this response to dopamine is dependent upon progesterone receptor as wild type mice given an anti-progestin fail to respond to administration of a specific D1 dopamine agonist.

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	From the Office of Dr. David Crews Focus of Research Note: (numbers in parentheses indicate publication number)
	1. Diversity and evolution of brain mechanisms controlling reproduction and behavior (MH R01 41770) Here I seek to (i) determine how stimuli relevant to reproduction are perceived and integrated in the central nervous system, (ii) demonstrate how the central nervous system regulates internal reproductive state, and (iii) examine how changes in internal state influence the expression of behavior (c.f., 85, 144, 209 and 225). Three animal model systems have been developed in the course of this research: the green anole lizard, the red-sided garter snake, and two species of whiptail lizards. This work has revealed that great diversity exists among vertebrates in reproductive behaviors and the neuroendocrine mechanisms underlying these behaviors. Comparisons of animals with different hormone-brain-behavior relationships suggest three factors which may explain species differences in endocrine physiology and behavior: (i) sensitivity to sex steroid hormones, (ii) hormone-dependent regulation of sex steroid hormone receptor gene expression, and (iii) neuroanatomical distribution of steroid receptor gene expression, especially in non-limbic structures. This work with reptiles has led us to re-examine certain assumptions in behavioral neuroendocrinology. One relevation concerns the idea that progesterone is a "female-specific" hormone with no function in males. We have found, however, that progesterone is vital to the display of male copulatory behavior in lizards as well as in mice and rats and, further, that androgen and progesterone synergize in males much like estrogen and progesterone synergize in females to facilitate sexual receptivity (c.f., 189 and 199). To study further the role of the progesterone and its receptor in the regulation of male sexual behavior, we have shown that male mice lacking the progesterone receptor (knockouts) show deficits in their mating behavior and sensitivity to androgen treatment (e.g., 237). This led recently to studies of the role of dopamine, a neurotransmitter implicated in both male and female sexual behavior We find that the progesterone receptor can be activated by dopamine independently of its natural ligand progesterone. Further, this response to dopamine is dependent upon progesterone receptor as wild type mice given an anti-progestin fail to respond to administration of a specific D1 dopamine agonist. (Back to Focus Main)