Influence of progesterone and GABAA receptor on calcium mobilization during human sperm acrosome reaction.
At fertilization, mammalian sperm has to undergo morphological changes of acrosome, namely acrosome reaction (AR), during which a dramatic increase of cytosolic calcium in consequence of extracellular calcium influx induces acrosomal exocytosis. It has been reported that progesterone is capable of inducing mammalian sperm AR. Several authors insisted that the agent, which was so far understood to bind with intracellular receptor, might act as an agonist against cell surface r-aminobutyric acid with type A (GABAA) receptor. The mode of action is, however, still in controversy. To investigate whether progesterone-induced AR is mediated by GABAA receptor, the present study examined pharmacologically the actions of progesterone on the morphological changes of acrosome and calcium mobilization during human sperm AR. Progesterone (15 microM) stimulated AR and increased cytosolic calcium, and the AR rate was further promoted by the coexistence of GABA (15 microM). Then these phenomena were suppressed by an antagonist of GABAA receptor (bicuculline, 10 microM), a blocker of GABAA receptor-coupled chloride channel (picrotoxin, 200 microM) and an antagonist of receptor-operated calcium channel (Lantan, 250 microM), respectively. These results indicated that the complex work of GABAA receptor-chloride channel and receptor operated calcium channel might participate in progesterone-induced AR and the transient increase of cytosolic calcium.
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. kurodayu@mb.kcom.ne.jp
Y
Y
Kuroda
S
S
Kaneko
Y
Y
Yoshimura
S
S
Nozawa
K
K
Mikoshiba
D020101:Acrosome Reaction / Q000187:drug effects / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003208:Concanavalin A; D003600:Cytosol / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006801:Humans; D007700:Kinetics; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013081:Sperm Motility; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001640:Bicuculline; D002118:Calcium; D002121:Calcium Channel Blockers; D003208:Concanavalin A; D016650:Fluorescein-5-isothiocyanate; D010852:Picrotoxin; D011374:Progesterone; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C042784:fluorescein isothiocyanate-concanavalin A