Vitellogenesis in reptiles as a model for mammalian sex-differentiated hepatic protein synthesis.

The stimulation of yolk protein synthesis by estrogen is a characteristic of female non-mammalian vertebrates; in mammals, or their reptilian ancestors, however, vitellogenesis has been suppressed as a corollary of the evolution of viviparity. It is our hypothesis that progesterone has a dual role in this phylogenetic trend: a) to inhibit myometrial contraction and thus set the stage for internal development of embryos and associated placentation and b) to inhibit yolk protein synthesis in a coordinate manner as placentation became an efficient direct supply of nutrients to the fetus. Despite the absence of vitellogenesis per se in eutherian mammals, significant sex-differentiated hepatic protein-lipid synthetic functions remain, which are under complex hormonal control. We have presented evidence that in the reptiles, the central vertebrate group from which the ancestors of modern mammals evolved, the control of yolk protein synthesis is also complex, involving both pituitary hormones (GH, PRL, and LH) and ovarian steroids (estradiol, testosterone, and progesterone). Adequate evidence exists to suggest that mammalian hepatic lipoprotein synthesis and its regulatory elements are phylogenetically derived from their reptilian ancestors and may be better understood in this context. This is of particular relevance to cardiovascular disease in which there is a clear sex bias yet for which no coordinated research program exists which takes into account the relevant phylogenetic history. We believe that reptilian, and possibly avian, models could be used to great advantage to probe the endocrine components of cardiovascular disease.