Behavioral Neuroendocrinology

 

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Biochemistry and Molecular Genetics 

Neuroscience Graduate Program

 

 

           

My research foci revolve around three main topics in Behavioral Neuroendocrinology. I study interactions between steroid hormone receptors as they pertain to sexual differentiation, and adult sexual performance and motivation. I am interested in genetic bases of sex differences in brain and behavior. Finally, I am investigating novel neural mechanisms that integrate nutritional and status and reproductive behaviors. Our work on the first two topics uses transgenic and knockout mice and for the third program we use musk shrews (Suncus murinus).

For representative publications, click here.

Steroid receptors and sexual behavior

In adulthood sex can be viewed as a motivated behavior that is regulated by testosterone. Testosterone is a pro-hormone and after it is metabolized it binds to one of three different steroid hormone receptors: androgen (AR), estrogen receptors (ER) α and/or β. Using transgenic mouse models we are dissecting the relative roles of these three receptors on sexual differentiation, performance, motivation and reward. We have made several important discoveries; one of these is that masculine sexual behavior does not require the action of ERα during development or in adults. The neurotransmitter dopamine can activate sexual behavior in male mice that lack functional ERα genes. This finding has moved the research into a different domain and again, using transgenic models we are studying the specific dopamine receptors that affect masculine sexual behavior. We are also starting a parallel program to examine female sexual behavior. A newer line of research in the lab involves the mechanisms of sexual differentiation. Sexual behaviors are classically defined as either "masculine" (e.g. mounting, thrusting, ejaculation) or "feminine" (e.g. lordosis, proceptive chases). Typically we think of the process by which animals show one but not the other types of sexual behaviors as a continuum, especially when we consider human behavior. However the way that we have studied the neural organization of these behaviors reflects our basis that males are both masculined and defeminized and females show the reverse complex. We are investigating the novel hypothesis that different steroid hormone receptors are activated in development to modulate different aspects of the adult sexual phenotype. This work is supported by NIH R01 MH57759.

Genetic Approaches to Sex Differences

The standard dogma taught in all undergraduate and graduate courses is that sex differences in brain and behavior are the result of developmental sex differences in steroid hormone concentrations in males and females. Males experience testosterone in late gestation and directly after birth whereas female ovaries are quiescent until puberty. Thus the model suggests, and decades of work support, the notion that the secretion of testosterone masculinizes the developing brain; in the absence of testosterone a feminine brain develops. We use knockout mice to assess the contributions of the genes for AR, ERα, ERβ, and the enzyme that converts testosterone to estradiol (aromatase) to the development and expression of neural sex differences. In addition, the classic model does not explain all sex differences in brain and behavior. An alternative hypothesis is that genes on the sex chromosomes (X and Y) are involved in neural sexual differentiation. Using transgenic and sex chromosome aneuploid mice we are identifying genes on the Y chromosome that have direct effects on sexually dimorphic behaviors. This work is supported by NIH R01 HD043196.

Interactions Between Reproduction and Nutrition

My work with musk shrews is centered on puberty and social induction of ovulation. Recently we have been interested in how nutrition enhances or blocks reproduction. We have shown that small perturbations in food intake can have dramatic and rapid effects on sexual behavior in female musk shrews. Nutrition is the universal cue that regulates reproductive effort in all mammals. Many mammals, including humans have at least two forms of gonadotropin releasing hormone (GnRH)

in brain. The major role of GnRH is as a releasing factor for the pituitary hormones LH and FSH, yet this second form (GnRH II) has only a weak effect on these hormones. We have recently discovered that GnRH II has a pivotal role as an interface between nutritional status and sexual behavior. When nutrition is limited GnRH II is depressed and females do not mate. When GnRH II is available females suppress food intake and begin mating, even if they are operating under reduced caloric intake. This finding shows that GnRH II may coordinate mating behavior with nutritional status in mammals. This work is supported by NIH R01 MH068729.