Hyenas: the “how” of female masculinization (Part 4)

Ambiguous genitalia at birth can be produce by genetic and/or hormonal causes. Genetic causes e.g. true hermaphrodites with gonads containing both female & male genes are very rare. More frequently ambiguous genitalia are caused by mutations in genes controlling sex hormone metabolism of the fetus or placenta. The mutations can for example increase testosterone production (input) or decrease testosterone breakdown (output). Sometimes external sources of hormones or their inhibitors can be the cause of abnormal genital development. For example a testosterone producing tumor in the mother or inhibition of testosterone action by chemicals contaminating of water supplies

Over 2000 years ago Aristotle stated a rumor that hyenas were hermaphrodites & “furnished with the organ both of the male & female” was untrue (Glickman et al 2006). However he had examined the striped hyena!  In the 4 members of the hyena family it is only the female spotted hyena (Crocuta crocuta) that displays the masculine external genitalia. Even in those days it was always important to always ask “is it true?” when reviewing scientific research!

Nevertheless the spotted hyena is not a hermaphrodite, but the female does have masculinized external genitalia. It is sometimes called a pseudo-hermaphrodite i.e. it is genetically a normal XX female with normal internal genitalia (ovaries &uterus) but external genitalia closely resembling the male (see part 1). The term pseudo-hermaphrodite has lost favor & ‘ambiguous genitalia” is the more commonly used term.

Let us first discuss the why their internal genitalia are normal despite the masculine external genitalia. The testis produces two hormones that influence the development of the male genitalia. Testosterone induces development of the penis & scrotum while anti-mullerian hormone inhibits development of the ovary, oviducts, & uterus. The female hyena does not have a testis to produce the two hormones. Thus without that sole source for anti-mullerian hormone her internal genitalia develop normally.  But the testis is not the only source of testosterone, it is also produced by the ovaries & adrenal glands. The fetal hyena ovaries & adrenals do produce testosterone but these organs only differentiate after the masculinization of the clitoris has occurred. So the testosterone is not derived from the fetus at that stage & would have to come from the mother’s ovaries or adrenals.

At present three mechanisms have been postulated  to explain the raised testosterone levels.  We will expand  our wash basin & lock & key models to try & simplify these ideas. (Figure 1)

testosterone metabolism female hyena fetus

Masculinization of the female hyena. Three possible mechanisms may produce raised testosterone levels in the fetus. (Click to enlarge)

  1. Maternal plasma testosterone levels are not higher than in other mammals but the SHBG  (sex hormone binding globulin) is much lower. Thus there is significantly more unbound testosterone in the mother’s plasma. This lipid soluble free hormone, unlike the protein bound testosterone, freely  crosses the placenta & masculinizes the female fetus (Hammond et al 2012)
  2. Hyena ovaries do produce large amounts of androstenedione , a testosterone precursor, & the hyena placenta in contrast to the human placenta does have abundant activity of a dehydrogenase enzyme to convert it to testosterone. This testosterone passes from the placenta on to the fetus (Glickman et al 2006)  .
  3. The third reason is related to an aromatase deficiency. This enzyme is present in mammalian placenta & converts testosterone to estradiol. Low levels were reported in the hyena placenta. This could cause raised fetal testosterone levels. However it is now known that the low levels are only develop in late pregnancy after the genitals are masculinized. Thus aromatase deficiency does not explain the development of male like external genitalia which is an early event in utero (Conley et al 2006). But it could explain the aggressive nature of the females as their developing brains would be exposed to high testosterone levels in utero in late pregnancy.

It is of interest to note that in man ambiguous genitalia can also occur from disturbances in the input or output in testosterone. The commonest cause is an enzyme deficiency in the adrenal gland where by estrogen production is blocked & its precursor is diverted to an excess input of testosterone i.e. adrenogenital syndrome. Rarer is the placental aromatase deficiency in which testosterone accumulates because of a decreased output as it cannot be converted to estradiol.

Reference: – Francis RC. 2004. Why men won’t ask for directions. The seductions of sociobiology. Princeton University Press.

Glickman SE et al. Mammalian sexual differentiation: lessons from the spotted hyena. Trends Endocrinol  Metabol 2006;17:349

Hammond et al. Phylogenetic Comparisons Implicate Sex Hormone-Binding Globulin in “Masculinization” of the Female Spotted Hyena (Crocuta crocuta). Endocrinology 2012;153:1435

A.J. Conley et al. Placental Expression and Molecular Characterization of Aromatase Cytochrome P450 in the Spotted Hyena (Crocuta crocuta). Placenta 2006;28:668

This entry was posted in Animal behavior, Biology, Physiology and tagged , , , . Bookmark the permalink.

Leave a Reply

Your email address will not be published. Required fields are marked *