Receptor structure, progesterone

We review below the major controversies dealing with PR structure including the functional significance of two hormone binding forms, the proteins comprising native holoreceptors, and the role of phosphorylation. 

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D. F. Smith, L. Whitesell, S. C. Nair, S. Y. Chen, V. Prapanich, and R. A. Rimerman. Progesterone receptor structure and function altered by geldanamycin, an Hsp90-binding agent. Mol Cell Biol, 15, 6804-6812, 1995. 

Because glucocorticoid receptor activity is not desirable yet is innate to those derivatives that bind with high affinity to the progesterone receptor, structural alterations have been investigated to pare out this biological activity. Small B-ring substituents serve to decrease glucocorticoid action, as do substituents at the C17 position. 

Sex Steroid Receptors Androgen Receptor, Estrogen Receptors, Progesterone Receptor. Figure 1 Schematic structures of AR, ERa, ER(3, and PR. 

The general steroid-receptor hypothesis is based mainly on estrogen and progesterone receptors. The currently accepted mechanism is unique and consists of several steps at different subcellular structures ... 

Fig. 2. Basic structure of receptors for progesterone (PR), glucocorticoid (GR), oestradiol (ER), thyroxine (T3) and vitamin D (Vit D). The receptors are divided into six domains, A-F [15] and the per-entage homology of region C for each receptor is compared with that for the progesterone receptor [9-14]. The number of amino acids in each receptor is shown on the right-hand side.

Winneker RC, Fensome A, Wrobel JE, Zhang Z, Zhang P. Nonsteroidal progesterone receptor modulators structure activity relationships. Semin. Reprod. Med. 2005 23 46-57. 

Churchill ME. Structure of the progesterone receptor-deoxyribonucleic acid complex novel interactions required for binding... 

Soederholm AA, Lehtovuori PT, Nyroenen TH. Docking and three-dimensional quantitative structure-activity relationship (3D QSAR) analyses of nonsteroidal progesterone receptor ligands. J Med Chem 2006 49 4261-8. 

Endometriosis-associated pain is secondary to structural and/or inflammatory causes. The lesions may cause pain by compression of nerve fibers. Increased pressure within endometriomas (cysts within the ovary) has been linked to dyspareunia. Endometrial lesions also generate local inflammation with prostaglandin release and increase the risk of developing adhesions. Endometrial lesions contain estrogen and progesterone receptors, and symptoms may correlate with the cyclic release of hormones during the menstrual cycle. 

So, S.-S., van Helden, S.P., van Geerestein, V.J. and Karplus, M. (2000) Quantitative structure-activity relationship studies of progesterone receptor binding steroids. /. Chem. Inf. Comput. ScL, 40, 762-772. 

Winneker, R.C., Fensome, A., Wrobel, J.E., Zhang, Z. and Zhang, P. (2005) Nonsteroidal progesterone receptor modulators structure-activity relationships. Seminars in Reproductive Medicine, 23, 46-57. 

Fig. 2.2.8. Structure of various organometallic steroids for potential radiodiagnostic and radiother-apeutic targeting of progesterone receptor (PR)- and estrogen receptor (ER)-positive cancer...

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