The cell surface progesterone receptor which stimulates calcium influx in human sperm is unlike the A ring reduced steroid site on the GABAA receptor/chloride channel.
Progesterone elicits a rapid, transient calcium influx in sperm that is a prerequisite for the progesterone-induced acrosome reaction. The possibility that the GABAA receptor/chloride channel was the receptor that mediated the progesterone-induced calcium influx in human sperm was examined. A-ring reduced 3 alpha-hydroxy pregnane steroids (e.g. alfaxalone, allopregnanolone, pregnanolone), which are active on the GABAA receptor/chloride channel, were found to be much weaker than progesterone at stimulating Ca2+ influx in sperm. The effects of a variety of progesterone metabolites and analogs and other steroids were compared for their ability to (i) stimulate GABA-induced 36Cl- uptake in synaptoneurosomes, (ii) stimulate GABA-induced Cl- currents in HEK-293 cells transfected with alpha 1, beta 2, and gamma 2 subunits of the GABAA receptor/chloride complex, and (iii) elicit a rapid Ca2+ influx in sperm. No correlation was observed between the ability of a given steroid to stimulate Ca2+ influx and efficacy in eliciting either 36Cl- uptake or chloride currents. Importantly, the action of progesterone to stimulate Ca2+ influx was not modified by GABA, diazepam, picrotoxin and pentobarbitol (known regulators of the GABAA receptor/chloride channel). It is concluded from these studies that the cell surface progesterone binding site on human sperm that mediates progesterone-induced changes in [Ca2+]i is unlike the steroid binding site on the GABAA receptor/chloride channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Blackmore
P F
PF
Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
Im
W B
WB
Bleasdale
J E
JE
D000177:Acrosome / Q000187:drug effects / Q000502:physiology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D006801:Humans; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011374:Progesterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002118:Calcium; D018118:Chloride Channels; D002712:Chlorides; D003975:Diazepam; D010424:Pentobarbital; D010852:Picrotoxin; D011374:Progesterone; D018079:Receptors, GABA; D011980:Receptors, Progesterone; D005680:gamma-Aminobutyric Acid