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Behavioral Neuroendocrinology |
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Alexander (Sasha) Kauffman |
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Dept. of Biochemistry and Molec. Genetics 1229 Jordan Hall 1300 Jefferson Park Ave Charlottesville, VA 22908 Phone Number: 434-982-4742 Fax Number: 434-243-8433 Email: ask5j@virginia.edu Download my CV here. Click here for non-science related stuff (i.e. pictures). |
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Research Description: My research focuses on the environmental and neuroendocrine regulation of behavior. The fitness of an animal is entirely dependent on its ability to successfully reproduce, a goal which is contingent on the effective coordination of behavior, physiology, and environmental factors. In most animals, energy availability is the ultimate factor in the regulation of reproduction, and the ability of animal to mate is thus tightly linked to its metabolic condition. One factor recently implicated in the coordination between energy availability and reproduction is the structural variant of gonadotropin-releasing hormone, GnRH II. This peptide is highly conserved across vertebrate species, from fish to mammals, and yet little information is known about its biological functions. While several studies have determined that GnRH II can promote LH secretion, it stimulates ovulation with much less potency than GnRH I (approximately 10% as effective), suggesting that this peptide?s main role is not to promote LH secretion. Instead, the neuroanatomical distribution of GnRH II, primarily in the mid-brain and extra-hypothalamic sites, suggests that the peptide may play a role as a neurotransmitter, perhaps in the regulation of behavior. In birds, infusion of GnRH II i.c.v. facilitates courtship displays in female song sparrows and ring doves. Furthermore, mammals may use GnRH II to integrate and regulate energy availability and reproduction. Female musk shrews which are food restricted for 48 hours exhibit significant decreases in mating behaviors. Central infusion of GnRH II, but not GnRH I, significantly reversed the inhibitory effects of food restriction on female shrew sex behavior. In contrast, GnRH II did not increase mating behavior in ad-libitum fed females, implying that this peptide's regulatory function is likely permissive rather than stimulatory. I extended this proposed role of GnRH II to other mammalian species which, in contrast to shrews, have regular estrous cycles (hormonal and behavioral). I determined that low food availability reduced female mouse mating behavior and that this deficit in mating can be reversed with the infusion of GnRH II. Thus, GnRH II appears to be acting as a permissive signal for reproduction, allowing sexual behavior only when enough food is available to support pregnancy and lactation. I also determined that these effects of GnRH II are not occurring via the type-1 GnRH receptor but rather through the type-2 receptor or other unidentified GnRH receptor. Because GnRH II levels vary with energy status in musk shrews, I also tested the hypothesis that, in addition to its permissive role in regulating reproduction, GnRH II might also act as a modulator of feeding and energy intake. Specifically, I postulated that if food is unavailable and a female is in negative energy balance, lower levels of GnRH II release might signal the animal to increase feeding and energy intake. Conversely, if there is abundant food available, the resulting higher levels of GnRH II secretion might be a signal to eat less (or at a baseline level). My findings in musk shrews supported this hypothesis. Specifically, food consumption decreased by 33% during the first 3 hours after GnRH II infusion. These effects seem to be mediated by the type-2 receptor, as blockade of the type-1 receptor does not prevent GnRH II from depressing feeding. In contrast, GnRH I had no effect on feeding in ad-lib females and only a minor effect in underfed females; food restriction may elevate type-2 receptors, thereby increasing sensitivity to GnRH I (which it can bond with low affinity). These findings are exciting as they posit a new biological function of GnRH II, which is to modulate energy intake; such feeding regulation complements the proposed role of GnRH II in regulating mating according to food availability. The goal of my current research is to further characterize the relationship between food availability, behavior, and GnRH II, and to determine the peptide's mechanism of action in the brain.
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