Progesterone and 17 alpha-hydroxyprogesterone. Novel stimulators of calcium influx in human sperm.
Progesterone and 17 alpha-hydroxyprogesterone (but not other steroids such as testosterone, corticosterone, beta-estradiol, estrone, dehydroepiandrosterone, 20 alpha-hydroxypregnen-3-one, androstenedione, and pregnenolone) were shown to cause an immediate increase, in free cytosolic calcium ([Ca2+]i) in both capacitated and noncapacitated human sperm, using the fluorescent indicator fura 2. Significant increases in [Ca2+]i were observed with 10 ng/ml progesterone, while maximum effects were seen with 1 microgram/ml progesterone. Two other steroids 11 beta-hydroxyprogesterone and 5 alpha-pregnane-3,20-dione exhibited significant activity to increase [Ca2+]i. This increase in [Ca2+]i elicited by progesterone was entirely due to Ca2+ influx from the extracellular medium since the increase in [Ca2+]i was blocked by the Ca2+ chelator EGTA (2.5 mM) and the Ca2+ channel antagonist La3+ (0.25 mM) when added to the medium containing 2.5 mM Ca2+. Progesterone also stimulated the uptake of Mn2+ into sperm as measured by the quenching of fura 2 fluorescence. Progesterone has been found in human follicular fluid at levels capable of stimulating increases in [Ca2+]i. The similarities in responses induced by human follicular fluid and progesterone an increase in [Ca2+]i, and hence the acrosome reaction, is progesterone and/or 17 alpha-hydroxyprogesterone. Progesterone (1 microgram/ml) did not increase [Ca2+]i in somatic cells such as adipocytes, hepatocytes, Balb/c 3T3 cells, normal rat kidney, or DDT1 MF-2 cells. The effects of these progestins to increase [Ca2+]i, by activating a receptor-operated calcium channel, is the first report of such an activity in sperm. This phenomena possibly opens up a new field of steroid action in the area of sterility, fertility, and contraception at the level of the sperm.
Blackmore
P F
PF
Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
Beebe
S J
SJ
Danforth
D R
DR
Alexander
N
N
D019326:17-alpha-Hydroxyprogesterone; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D006908:Hydroxyprogesterones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D013094:Spermatozoa / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D013997:Time Factors
D006908:Hydroxyprogesterones; D013256:Steroids; D008345:Manganese; D011374:Progesterone; D004533:Egtazic Acid; D019326:17-alpha-Hydroxyprogesterone; D007811:Lanthanum; D002118:Calcium