Androgens and masculinization of genitalia in the spotted hyaena (Crocuta crocuta). 2. Effects of prenatal anti-androgens

Abstract

Pregnant spotted hyaenas were treated with anti-androgens to interfere with the unusually masculine 'phallic' development that characterizes females of this species. The effects on genital morphology and plasma androgen concentrations of infants were studied during the first 6 months of life. Although there were consistent 'feminizing' effects of prenatal anti-androgen treatment on genital morphology in both sexes, such exposure did not produce males with extreme hypospadia, as it does in other species, nor did it produce females with a 'typical' mammalian clitoris and external vagina. 'Feminization' of males resulted in a penis with the morphological features of the hyaena clitoris, and 'feminization' of females exaggerated the sex differences that are typical of this species. The effects of treatment were present at birth and persisted for at least 6 months. Treatment of pregnant females with flutamide and finasteride also markedly reduced circulating concentrations of testosterone and dihydrotestosterone in maternal plasma during pregnancy. Plasma delta 4-androstenedione was reduced in the female, but not the male, infants of treated mothers, consistent with an epigenetic hypothesis previously advanced to explain hormonal 'masculinization' of females. The present 'feminizing' effects of prenatal anti-androgen treatment are consistent with contemporary understanding of sexual differentiation, which accounts for morphological variation between the sexes in terms of steroids. However, current theory does not account for the basic genital structure of females and the present data suggest that development of the male penis and scrotum, and the female clitoris and pseudoscrotum, in spotted hyaenas may involve both androgen-dependent and androgen-independent components.

Exposure to naturally circulating androgens during foetal life incurs direct reproductive costs in female spotted hyenas, but is prerequisite for male mating

“…In addition, experimental males maintained a rounded rather than angular contour in the shape of their glans, evident during erections (see fig. 2b in Drea et al 1998). At the age when males normally mate for the first time (24 months), experimental animals were equipped with a shorter (t 10 = 4.72, p Ͻ 0.001) thicker (t 17 = 2.96, p Ͻ 0.01) and more rounded penis than controls.…”

Adaptation, Exaptation, and Constraint: A Hormonal Perspective

“…For example, chemical treatment of pregnant spotted hyenas with antiandrogens produces a shorter, thicker clitoris in their offspring, but the modified structure is nevertheless large and erectile and quite unlike the clitoris of a typical mammal ). This finding implies that full development of the peniform clitoris involves not simply early androgen exposure but also the action of steroid-independent mechanisms in the target tissue (Foster et al 1996;Drea et al 1998;Glickman et al 1998;Licht et al 1998). If so, and if the genes responsible for elaboration of the clitoris came to be favored after the penile form originated, then Gould and Vrba's (1982) conclusion that the penile clitoris of the female spotted hyena is simply an unselected indirect effect of selection for other masculine traits might require reexamination (West-Eberhard 1992a).…”

Endocrine differentiation of fetal ovaries and testes of the spotted hyena (Crocuta crocuta): timing of androgen-independent versus androgen-driven genital development

“…Both male and female gonads were proposed to be sites of androgen synthesis during fetal life from studies on field specimens (Lindeque & Skinner 1982). However, fetal ages were likely underestimated, based on the examination of more accurately staged tissues from pairing and/or observed mating dates (Licht et al 1998). Licht et al suggested that androgen from the fetal ovary might perhaps influence clitoral development later during gestation, but considered it highly unorganized at stages early enough to influence genital tubercle morphogenesis (Licht et al 1998).…”

“…However, fetal ages were likely underestimated, based on the examination of more accurately staged tissues from pairing and/or observed mating dates (Licht et al 1998). Licht et al suggested that androgen from the fetal ovary might perhaps influence clitoral development later during gestation, but considered it highly unorganized at stages early enough to influence genital tubercle morphogenesis (Licht et al 1998). More recent studies showed that genital tubercle differentiation is not only sexually dimorphic (Cunha et al 2003) but also androgen sensitive (Cunha et al 2005).…”

“…More recent studies showed that genital tubercle differentiation is not only sexually dimorphic (Cunha et al 2003) but also androgen sensitive (Cunha et al 2005). The penis is longer and thicker than the clitoris (Frank et al 1990), with an angular (rather than a rounded) glans, and a narrower, less elastic urogenital meatus (Frank et al 1990, Drea et al 1998. Internally, there are also sex differences in positioning of the retractor muscles, location of erectile tissues and surrounding fibroelastic tunica, and 'pleating' of the urogenital sinus (Neaves et al 1980, Cunha et al 2003, 2005.…”