The sex steroids and the peptide hormone oxytocin are both ancient modulato
rs of the reproductive system of most metazoan species responsible for tiss
ue differentiation and acute events respectively. In vivo experimentation i
mplies estrogenic control of both the oxytocin (OT) gene and that for its r
eceptor (OTR). Yet neither gene promoter appears able to bind classic estro
gen-dependent nuclear receptors (ER) in vitro. The literature is confused b
y some transfected cell culture experiments which suggest that the human an
d rat OT gene promoter can be regulated by both ER alpha and ER beta throug
h a major hormone response element at - 160 bp upstream of the transcriptio
n start site. These findings depended, however, upon the presence of a high
molar excess of the nuclear estrogen receptor. The current consensus sugge
sts that the sex steroids are acting indirectly on both the OT and OTR gene
s, possibly involving intermediate transcription factors or cofactors. They
may also act upon the OTR at the cell membrane, though more study is neede
d before the few current observations can be generalized. Due to the OT sys
tem being so ancient and fundamental to all aspects of reproduction, it is
likely that the mechanisms by which the sex steroids influence this system
are going to be of general importance to many other basic aspects of reprod
uctive control. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.