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BOR - Papers in Press, published online ahead of print May 25, 2005.
Biol Reprod 2005, 10.1095/biolreprod.105.041129
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BIOLOGY OF REPRODUCTION 73, 554–564 (2005)
DOI: 10.1095/biolreprod.105.041129
© 2005 by the Society for the Study of Reproduction, Inc.

The Ontogeny of the Urogenital System of the Spotted Hyena (Crocuta crocuta Erxleben)1

Gerald R. Cunha 2, 3,4 , Ned J. Place 5, Larry Baskin 4, Alan Conley 6, Mary Weldele 5, Tristan J. Cunha 3, Y.Z. Wang 7, Mei Cao 3,4 , and Stephen E. Glickman 5

Departments of Anatomy3 Urology,4 University of California, San Francisco, California 94143 Department of Psychology,5 University of California, Berkeley, California 94720 Department of Population Health & Reproduction,6 School of Veterinary Medicine, University of California, Davis, California 95616 BC Cancer Agency,7 Department of Cancer Endocrinology, Vancouver, British Columbia, Canada V5Z 4E6

Studies were conducted to elucidate the importance of androgen-mediated induction of the extreme masculinization of the external genitalia in female spotted hyenas. Phallic size and shape; androgen receptor (AR) and {alpha}-actin expression; and sex-specific differences in phallic retractor musculature, erectile tissue, tunica albuginea, and urethra/urogenital sinus were examined in male and female fetuses from Day 30 of gestation to term. Similar outcomes were assessed in fetuses from dams treated with an AR blocker and a 5{alpha}-reductase inhibitor (antiandrogen treatment). Clitoral and penile development were already advanced at Day 30 of gestation and grossly indistinguishable between male and female fetuses throughout pregnancy. Sex-specific differences in internal phallic organization were evident at Gestational Day 45, coincident with AR expression and testicular differentiation. Antiandrogen treatment inhibited prostatic development in males and effectively feminized internal penile anatomy. We conclude that gross masculinization of phallic size and shape of male and female fetuses is androgen-independent, but that sexual dimorphism of internal phallic structure is dependent on fetal testicular androgens acting via AR in the relevant cells/tissues. Androgens secreted by the maternal ovaries and metabolized by the placenta do not appear to be involved in gross masculinization or in most of the sex differences in internal phallic structure.

androgen receptor, clitoris, developmental biology, female urogenital tract, male urogenital tract, penis, spotted hyena, testosterone


1 Supported by National Institutes of Health grant MH-39917 and HD-08729.

2 Correspondence: Gerald R. Cunha, Department of Anatomy, University of California, 3rd and Parnassus, San Francisco, CA 94143. FAX: 415 502 2270; grcunha{at}itsa.ucsf.edu




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P Browne, N J Place, J D Vidal, I T Moore, G R Cunha, S E Glickman, and A J Conley
Endocrine differentiation of fetal ovaries and testes of the spotted hyena (Crocuta crocuta): timing of androgen-independent versus androgen-driven genital development.
Reproduction, October 1, 2006; 132(4): 649 - 659.
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Copyright © 2005 by the Society for the Study of Reproduction.