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Proteins secreted from the early ovine conceptus block the action of prostaglandin F2 alpha on large luteal cells.

In this study we evaluated whether the early conceptus secretes a factor that blocks the action of prostaglandin (PG) F2 alpha on cultured ovine large luteal cells. PGF2 alpha inhibited progesterone production by lipoprotein-stimulated large luteal cells and this anti-steroidogenic action was blocked in a dose-dependent manner by conceptus proteins secreted from Day 15 embryos. Purified ovine trophoblast protein-1 (oTP-1) did not exhibit the anti-PGF2 alpha activity, but secreted conceptus proteins devoid of oTP-1 did prevent the anti-steroidogenic effects of PGF2 alpha. This activity does not appear to be a nonspecific effect of protein since neither serum albumin nor thyroglobulin, gamma globulin, insulin, LH, secreted ovine endometrial proteins, or heat-inactivated secreted conceptus proteins had this action. After molecular-sizing chromatography we found a high- and a low-molecular weight fraction with luteal protective activity. Neither of the secreted conceptus protein fractions blocked the binding of 3H-PGF2 alpha to large luteal cells. However, conceptus proteins did block the anti-steroidogenic action of phorbol ester and calcium ionophore on large luteal cells, suggesting that secreted conceptus proteins act after activation of the free calcium/protein kinase C intracellular effector pathways. Thus, the early ovine conceptus secretes a luteal protective protein(s) that may be important for maintaining the corpus luteum during early pregnancy; however, the physiologic significance of this luteal protective protein(s) cannot be stated without further investigation.