Highly purified chicken progesterone receptor (cPR) is shown to stimulate RNA synthesis directly in an in vitro transcription assay. Stimulation of transcription by cPR requires the presence of progesterone response elements (PREs) in the template and can be specifically inhibited by addition of competitor oligonucleotides containing PREs. Binding of receptor to two PREs is cooperative and leads to synergistic (27-fold) stimulation of transcription. A purified fusion protein containing the DNA binding domain of cPR linked to yeast ubiquitin was produced in E. coli and also functions in the transcription assay. Using this in vitro transcription system, we demonstrate that hormone-free cPR activated by salt treatment induces transcription of a test gene in a hormone-independent manner. Finally, we present evidence that the progesterone receptor acts by facilitating the formation of a stable preinitiation complex at the target gene promoter and thus augments the initiation of transcription by RNA polymerase II.

Animals↗

PubMed1990

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.

Animals↗

PubMed1990

Psychogenic dyskinesias in patients with organic movement disorders.

The association of psychogenic neurological features with organic neurological disease is commonly acknowledged. However, the occurrence of psychogenic dyskinesias in patients with underlying organic movement disorders is not well recognized. Six cases of psychogenic dyskinesias complicating preexisting organic movement disorders are described. This possibility must be carefully considered and excluded before an unusual movement disorder can be considered entirely psychogenic.

Adult↗

PubMed1990

Vertebrate vitellogenesis: molecular model for multihormonal control of gene regulation.

The stimulation of yolk protein synthesis by estrogen is a characteristic of female non-mammalian vertebrates; in mammals, 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, b) to inhibit yolk protein synthesis as placentation became an efficient direct supply of nutrients to the fetus. 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 complex, involving both pituitary and ovarian steroids (estradiol, testosterone and progesterone). This system provides an excellent model for the multihormonal contents of gene regulation involving both + and - controls.

Animals↗

PubMed1989