Biochemistry of aromatase: significance to female reproductive physiology

Abstract

The formation of estrogens in mammals via aromatase involves the relatively unique capacity to form an aromatic ring de novo in contrast to most other aromatic substances (essential amino acids) which are obtained only in the diet. The reaction is the only example of a cytochrome P450 system which resides in both the mitochondrial and microsomal fractions of the cell. It occurs widely throughout the body in diverse tissues and functions via both de novo synthesis and transformation of prehormones (androstenedione and testosterone). It is found widely in animal species in both the brain and gonads even in phylogenetically primitive species. Placental aromatase appears to be associated with the evolution of viviparity and an extended gestational period in utero. Follicular aromatase which is dependent upon follicle-stimulating hormone stimulation appears to be essential for oogenesis, ovulation, and normal luteal functions while central nervous system aromatase serves to determine sexual behavior and the neurohormonal link to the hypothalamus and pituitary for ovarian cyclicity. While estrogens are the key to pituitary, breast, and endometrial growth and development, this hormone is one of the few examples of an endogenous steroid that has been implicated as a carcinogen or a stimulant for carcinogenesis.