Synthetic progestins: in vitro potency on human endometrium and specific binding to cytosol receptor

Area of Science:

• Endocrinology
• Reproductive Biology
• Pharmacology

Background:

• Synthetic progestins are widely used in hormone therapy.
• Understanding their relative potencies and affinities is crucial for clinical application.
• Human endometrial organ culture provides a model for evaluating progestin effects.

Purpose of the Study:

• To compare the relative potencies of six common synthetic progestins in human endometrium.
• To assess the binding affinities of these progestins to the endometrial progesterone receptor.
• To correlate in vitro receptor affinity with in vivo tissue response.

Main Methods:

• Human endometrial tissue was cultured in vitro.
• Progestin-induced changes in tissue glycogen were measured.
• Progesterone receptor affinities were determined using spheroidal hydroxylapatite chromatography after CBG-like protein removal.

Main Results:

• All six synthetic progestins increased endometrial glycogen at lower concentrations than progesterone.
• Medroxyprogesterone acetate was the only progestin with a relative affinity greater than progesterone.
• The relative order of potency and affinity was consistent across progestins, but magnitudes differed.

Conclusions:

• Synthetic progestins exhibit varying potencies and receptor affinities in human endometrium.
• Medroxyprogesterone acetate demonstrates a distinct affinity profile.
• These findings highlight the importance of considering both potency and affinity for synthetic progestin selection.