Gonadotropins and the uterus: Is there a gonad-independent pathway?

In the gonads, LH and hCG act via the same receptor to stimulate the production of progesterone in the luteal phase of the menstrual cycle and in early pregnancy. There are numerous reports that these two hormones can have direct actions on the uterus in addition to their indirect actions via stimulation of ovarian steroid hormones. However, unlike the situation in the gonads, various uterine tissues have been shown to respond to the related hormones FSH and TSH or the α-subunit common to these hormones. These additional actions cannot be mediated by the gonadal LH/hCG receptor. There have also been a series of reports that the uterus contains LH/hCG receptors. Attempts to characterize the molecular structure of these receptors have been difficult; thus, the possibility of a variant receptor cannot be excluded. The possibility also exists of a nonhomologous receptor, which would explain the differences in ligand specificity in uterine tissues. I will review the evidence regarding gonadotropin action in nongonadal tissues, primarily the uterus. In addition, the data regarding receptors will be reviewed. Finally, the clinical areas informed by this information will be explored.