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


METHODS
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.


CONCLUSIONS
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.
Attardi
Barbara J
BJ
Molecular Endocrinology Laboratory, Bioqual, Inc, Rockville, MD, USA.
Zeleznik
Anthony
A
Simhan
Hyagriv
H
Chiao
Jye Ping
JP
Mattison
Donald R
DR
Caritis
Steve N
SN
D000077713:17 alpha-Hydroxyprogesterone Caproate; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D006908:Hydroxyprogesterones / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
D006908:Hydroxyprogesterones; D011372:Progestins; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D000077713:17 alpha-Hydroxyprogesterone Caproate; D011374:Progesterone