This research project involves the study of a very unusual animal, the spotted hyena (Crocuta crocuta), in order to understand general processes of sexual differentiation and the role of naturally circulating androgens in female mammals. Female spotted hyenas have the most highly """"""""masculinized"""""""" genitalia of any mammalian species. There is no external vagina. The clitoris has developed until it is the approximate size and shape of the male penis and is traversed by a central urogenital canal through which the female hyena urinates, copulates and gives birth. These social carnivores live in multi-female, multi-male clans and, within these clans, adult females are very aggressive, totally dominating adult males who arrive in the clan as immigrants. Contemporary understanding of sexual differentiation requires that androgens circulate during fetal life in order to produce the """"""""masculinized"""""""" genitalia of female spotted hyenas. Such androgens might also be expected to facilitate female aggression. In prior grant periods the investigators (1) identified ovarian androstenedione as the primary circulating androgen in female hyenas, and (2) found that it was converted by the placenta to testosterone and transferred to the fetus. This provides a route for maternal """"""""masculinization"""""""" of her daughters, which has now appeared in the human medical literature. Four lines of research are proposed for the next grant period: (1) Experiments in which anti-androgens are supplied to pregnant females, designed to determine the maximal possible effect of such treatment on urogenital development, postnatal steroid secretion and social behavior. (2) Investigations of normal fetal urogenital development and steroid influences during the earliest stages of sexual differentiation. (3) Studies of structures/systems in the hyena Central Nervous System, which are sexually dimorphic in other species, in order to determine the extent to which such differences are attenuated, or reversed, in hyenas due to the high concentrations of pre- and post-natal androgen circulating in both sexes. (4) Studies of exogenous steroids supplied to ovariectomized female hyenas in order to determine whether the exceptional aggressiveness of female hyenas toward males, and the high levels of affiliative behavior observed in dominant females, is due to ovarian secretion of estradiol and/or androstenedione.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH039917-15
Application #
2890326
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Program Officer
Oliveri, Mary Ellen
Project Start
1984-06-01
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Cunha, Gerald R; Risbridger, Gail; Wang, Hong et al. (2014) Development of the external genitalia: perspectives from the spotted hyena (Crocuta crocuta). Differentiation 87:4-22
Hammond, Geoffrey L; Miguel-Queralt, Solange; Yalcinkaya, Tamer M et al. (2012) Phylogenetic comparisons implicate sex hormone-binding globulin in ""masculinization"" of the female spotted hyena (Crocuta crocuta). Endocrinology 153:1435-43
Place, Ned J; Coscia, Elizabeth M; Dahl, Nancy J et al. (2011) The anti-androgen combination, flutamide plus finasteride, paradoxically suppressed LH and androgen concentrations in pregnant spotted hyenas, but not in males. Gen Comp Endocrinol 170:455-9
Van Meter, Page E; French, Jeffrey A; Bidali, Kaisa et al. (2008) Non-invasive measurement of fecal estrogens in the spotted hyena (Crocuta crocuta). Gen Comp Endocrinol 155:464-71
Athirakul, Krairerk; Bradbury, J Alyce; Graves, Joan P et al. (2008) Increased blood pressure in mice lacking cytochrome P450 2J5. FASEB J 22:4096-108
Wagner, Aaron P; Frank, Laurence G; Creel, Scott et al. (2007) Transient genital abnormalities in striped hyenas (Hyaena hyaena). Horm Behav 51:626-32
Glickman, Stephen E; Cunha, Gerald R; Drea, Christine M et al. (2006) Mammalian sexual differentiation: lessons from the spotted hyena. Trends Endocrinol Metab 17:349-56
McFadden, Dennis; Pasanen, Edward G; Weldele, Mary L et al. (2006) Masculinized otoacoustic emissions in female spotted hyenas (Crocuta crocuta). Horm Behav 50:285-92
Drea, Christine M (2006) Studying primate learning in group contexts: Tests of social foraging, response to novelty, and cooperative problem solving. Methods 38:162-77
Browne, P; Place, N J; Vidal, J D et al. (2006) Endocrine differentiation of fetal ovaries and testes of the spotted hyena (Crocuta crocuta): timing of androgen-independent versus androgen-driven genital development. Reproduction 132:649-59

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