Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins.

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Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN

Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins.

Am J Obstet Gynecol. 2007 Dec;197(6):599.e1-7.

PubMed ID

18060946 [ View in PubMed

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Abstract

OBJECTIVE: This study was undertaken to determine whether the reduction in premature birth attributable to 17-alpha hydroxyprogesterone caproate occurs because of a greater affinity for progesterone or glucocorticoid receptors or by enhanced stimulation of progestogen responsive genes when compared with progesterone. STUDY DESIGN: We performed competitive steroid hormone receptor binding assays using cytosols expressing either recombinant human progesterone receptor-A or -B or rabbit uterine or thymic cytosols. We used 4 different carcinoma cell lines to assess transactivation of reporter genes or induction of alkaline phosphatase. RESULTS: Relative binding affinity of 17-alpha hydroxyprogesterone caproate for recombinant human progesterone receptor-B, recombinant human progesterone receptor-A, and rabbit progesterone receptors was 26-30% that of progesterone. Binding of progesterone to rabbit thymic glucocorticoid receptors was weak. 17-alpha hydroxyprogesterone caproate was comparable to progesterone in eliciting gene expression in all cell lines studied. CONCLUSION: Binding to progesterone receptors, glucocorticoid receptors, or expression of progesterone-responsive genes is no greater with 17-alpha hydroxyprogesterone caproate than with progesterone. Other mechanisms must account for the beneficial effect of 17-alpha hydroxyprogesterone caproate on preterm birth rates.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Progesterone	Glucocorticoid receptor	Protein	Humans	Unknown	Partial agonist	Details