Extragenomic actions of progesterone in human sperm and progesterone metabolites in human platelets

Steroids. Jan-Feb 1999;64(1-2):149-56. doi: 10.1016/s0039-128x(98)00109-3.

Abstract

Progesterone rapidly increased intracellular free calcium ([Ca2+]i) in human sperm, removal of extracellular Ca2+ prevented the increase in [Ca2+]i. The Ca2+ influx was not blocked by the T-type Ca2+ channel blocker mibefradil. However T-type calcium channels do appear to be present in human sperm because the neoglycoprotein mannose-albumin, an inducer of the acrosome reaction, was able to promote Ca2+ influx, which was blocked by mibefradil and more potently inhibited by Ni2+ than Cd2+. The receptor for progesterone that promotes the Ca2+ influx was located on the plasma membrane using FITC-progesterone-albumin. It is concluded that progesterone stimulates Ca2+ influx in human sperm via a unique Ca2+ channel possibly similar to a store-operated channel (SOC) or a receptor-operated channel (ROC). We have found that progesterone metabolites, such as pregnanolone and pregnanediol, promote a rapid rise in [Ca2+]i and aggregation in human platelets, similar to that observed with thrombin. The increase in [Ca2+]i was prevented when extracellular Ca2+ was removed or by the SOC inhibitor SKF-96365. The phospholipase C inhibitor U-73122 also prevented the increase in [Ca2+]i, suggesting that these metabolites interact with a cell surface receptor on the platelet to activate phospholipase C to produce inositol-P3, which mobilizes intracellular Ca2+, thereby activating the SOC in the plasma membrane. Progesterone and estradiol conjugated to albumin, also produced a rapid increase in [Ca2+]i, which was prevented by Ca2+ removal from the medium or when SKF-96365 or U-73122 were added. It is proposed that human platelets possess cell surface receptors for steroids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Platelets / metabolism*
  • Calcium / blood
  • Calcium Channels / metabolism
  • Estrogens / metabolism
  • Humans
  • Male
  • Progesterone / metabolism
  • Progesterone / physiology*
  • Progesterone-Binding Globulin / metabolism
  • Protein Binding
  • Serum Albumin / metabolism
  • Spermatozoa / physiology*

Substances

  • Calcium Channels
  • Estrogens
  • Progesterone-Binding Globulin
  • Serum Albumin
  • Progesterone
  • Calcium