First messenger regulation of mammalian sperm function via adenylyl cyclase/cAMP.
When released into an appropriate environment, mammalian spermatozoa begin to capacitate and then continue until fully capacitated and able to fertilize. During capacitation in vitro, some cells 'over-capacitate' and undergo spontaneous acrosome reactions; this would be highly undesirable in vivo since already acrosome-reacted spermatozoa are non-fertilizing. Recent studies have revealed that seminal plasma contains several small molecules that bind to specific receptors on the sperm plasma membrane and act as 'first messengers', causing biologically important changes in availability of the 'second messenger' cAMP. Fertilization promoting peptide (FPP), calcitonin and adenosine all regulate cAMP production, stimulating it in uncapacitated spermatozoa and then inhibiting it in capacitated cells; in contrast, angiotensin II stimulates cAMP throughout capacitation. The molecules that regulate cAMP appear to do so via G protein-modulated changes in membrane associated adenylyl cyclases (mACs). Both mouse and human spermatozoa have been shown to have Galphas and Galphai2, as well as several isoforms of mAC, located in the same regions as the specific receptors. Thus spermatozoa possess the required elements for several separate signal transduction pathways, many of which regulate mAC/cAMP and so maintain sperm fertilizing ability. In vivo, such responses could increase the chances of successful fertilization.
Fraser
Lynn R
LR
Reproduction and Rhythms Group, Centre for Reproduction, Endocrinology and Diabetes, School of Biomedical Sciences, King's College London, Guy's Campus, London, UK. lynn.fraser@kcl.ac.uk
Adeoya-Osiguwa
Susan
S
Baxendale
Rhona W
RW
Mededovic
Samra
S
Osiguwa
Olufunmilayo O
OO
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000804:Angiotensin II / Q000737:chemistry; D000818:Animals; D002116:Calcitonin / Q000737:chemistry / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D015398:Signal Transduction; D013075:Sperm Capacitation; D013094:Spermatozoa / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry
D000804:Angiotensin II; D013973:Thyrotropin-Releasing Hormone; C059697:pyroglutamyl-glutamyl-proline amide; D002116:Calcitonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D011761:Pyrrolidonecarboxylic Acid