The goal of the proposed research is to elucidate the role of steroid hormones in controlling sexually dimorphic behaviors. Male-typical copulatory behaviors such as mounting and intromission are dependent on androgens in all vertebrates studied, but the mechanisms by which these hormones influence the brain and behavior are not well understood. Whiptail lizards of the genus Cnemidophorus enable a powerful comparative approach to understanding these mechanisms because some species are sexual, exhibiting the typical vertebrate pattern of sexually dimorphic behavior (estrogen-dependent receptivity in females and androgen-dependent mounting in males), and other species are all-female, reproducing clonally and exhibiting both male-like and female-like behavior, according to ovarian hormone levels. The experiments proposed involve C. inornatus, a typical sexual species, and C. uniparens, which is all-female. C. uniparens individuals, just like C. inornatus females, are receptive when their circulating estrogen levels are high, but unlike C. inornatus, they also exhibit the complete repertoire of male-typical copulatory behavior when presented with a receptive female during the periovulatory phase of the ovarian cycle when progesterone levels are high. This """"""""pseudocopulatory"""""""" behavior can be evoked in the laboratory by administration of exogenous progesterone, and the operational goal of this research is to determine how progesterone is able to mimic the normal function of androgen in this way. Specific experiments will investigate how the progesterone receptor comes to be expressed in the preoptic area of the brain that is thought to mediate male-typical copulatory behavior, and in the process will yield information about the normal function of this area, as well as the developmental regulation of steroid hormone receptors. Other studies will elucidate the actions of androgens and progesterone on the neurotransmitters dopamine and nitric oxide, which are important components in the neural control of sexual behavior. This functional interchangeability of androgens and progestins has obvious fundamental implications for human health. All women normally experience fluctuating levels of progesterone, and millions of women use exogenous progestins. There is also a marked diurnal rhythm [in] progesterone levels in men, and progestins (usually in conjunction with testosterone) are beginning to be studied as a male contraceptive. The interaction of these progestins with the functions of other steroid hormones therefore warrants thorough investigation. From a scientific point of view, the hormonal control of sexual behavior is a particularly tractable model for elucidating the way in which particular genes, expressed in particular neural circuits, can affect specific behaviors, because the stimuli and behaviors involved are simple, the brain areas involved are well characterized, and the relationship between hormones and genes is comparatively well understood.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH041770-23
Application #
7531821
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Simmons, Janine M
Project Start
1986-09-01
Project End
2010-11-30
Budget Start
2008-12-01
Budget End
2010-11-30
Support Year
23
Fiscal Year
2009
Total Cost
$320,012
Indirect Cost
Name
University of Texas Austin
Department
Neurology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Crews, David (2013) Binary outputs from unitary networks. Integr Comp Biol 53:888-94
O'Connell, L A; Mitchell, M M; Hofmann, H A et al. (2012) Androgens coordinate neurotransmitter-related gene expression in male whiptail lizards. Genes Brain Behav 11:813-8
Crews, David (2011) Epigenetic modifications of brain and behavior: theory and practice. Horm Behav 59:393-8
O'Connell, Lauren A; Matthews, Bryan J; Patel, Sagar B et al. (2011) Molecular characterization and brain distribution of the progesterone receptor in whiptail lizards. Gen Comp Endocrinol 171:64-74
O'Connell, L A; Matthews, B J; Crews, D (2011) Neuronal nitric oxide synthase as a substrate for the evolution of pseudosexual behaviour in a parthenogenetic whiptail lizard. J Neuroendocrinol 23:244-53
Ramsey, Mary; Crews, David (2009) Steroid signaling and temperature-dependent sex determination-Reviewing the evidence for early action of estrogen during ovarian determination in turtles. Semin Cell Dev Biol 20:283-92
Shoemaker, Christina M; Crews, David (2009) Analyzing the coordinated gene network underlying temperature-dependent sex determination in reptiles. Semin Cell Dev Biol 20:293-303
Dias, Brian George; Chin, Sonia Grace; Crews, David (2009) Steroidogenic enzyme gene expression in the brain of the parthenogenetic whiptail lizard, Cnemidophorus uniparens. Brain Res 1253:129-38
Dias, Brian George; Crews, David (2008) Regulation of pseudosexual behavior in the parthenogenetic whiptail lizard, Cnemidophorus uniparens. Endocrinology 149:4622-31
Crews, David (2008) Epigenetics and its implications for behavioral neuroendocrinology. Front Neuroendocrinol 29:344-57

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