Progestin withdrawal at parturition in the mare.

Area of Science:

• Reproductive Endocrinology
• Comparative Physiology
• Steroid Biochemistry

Background:

• Mammalian pregnancy requires progesterone for maintenance, and parturition necessitates its withdrawal.
• In mares, progesterone levels are low during pregnancy, suggesting other progestins play a role.
• 5α-dihydroprogesterone (DHP) exhibits progestogenic bioactivity, prompting a re-evaluation of progestin withdrawal at foaling.

Purpose of the Study:

• To investigate the concentrations and bioactivity of various pregnanes in periparturient mares.
• To determine the role of DHP and its metabolites in supporting equine pregnancy.
• To elucidate the mechanism of progestin withdrawal preceding parturition in mares.

Main Methods:

• Liquid chromatography-mass spectrometry was used to monitor systemic pregnane concentrations in mares (n=7) for 10 days prior to foaling.
• Luciferase reporter assays assessed the biopotency of dominant pregnane metabolites using Chinese hamster ovarian cells expressing the equine progesterone receptor (ePGR).
• Cells were incubated with varying concentrations of progesterone, 20α-hydroxy-5α-dihydroprogesterone (20αDHP), and 3α,20β-dihydroxy-5α-pregnane (3α,20βDHP).

Main Results:

• Circulating pregnane concentrations were highest for 3α,20βDHP and 20αDHP, followed by DHP and allopregnanolone, with pregnenolone and progesterone being the lowest.
• All measured pregnanes decreased by approximately 50% from their prepartum peaks to the day before foaling.
• While progesterone showed maximum equine progesterone receptor (ePGR) activation at 30nM, 20αDHP and 3α,20βDHP demonstrated significant ePGR activation at their respective prepartum concentrations, despite lower biopotency compared to progesterone.

Conclusions:

• Progestogenic support for pregnancy in mares declines 3-5 days before foaling.
• DHP is the major progestin based on prepartum peak concentrations.
• Other pregnanes, particularly 20αDHP, are present in sufficient concentrations to exert physiological effects in the absence of DHP, indicating a complex progestin withdrawal mechanism involving placental synthesis cessation.