A novel functional estrogen receptor on human sperm membrane interferes with progesterone effects
Introduction
Increasing evidence indicates that specific cell membrane receptors are involved in rapid effects of steroids (Wehling, 1997). As far as estrogens concerns, non-genomic effects of 17βE2 have been demonstrated on intracellular calcium concentrations ([Ca2+]i), cyclic adenosine monophosphate levels (cAMP), mitogen activated protein kinase activity, phospholipase C and A2, protein kinase C in different tissues and cell lines (Nemere and Farach-Carson, 1998). Estrogens are present at micromolar concentrations in follicular fluid (Frederick et al., 1991), a location that suggests a possible role of these molecules in the regulation of male and female gamete function. However, while several studies have demonstrated rapid effects of 17βE2 in human oocytes and documented its role in oocyte activation and development (for review see Revelli et al., 1998), little is known about the estrogen effects in spermatozoa (Revelli et al., 1998). The influence exerted by the lack of estrogen receptors on sperm function in estrogen receptor knock-out (ERKO) mice have been recently investigated (Couse and Korach, 1999), showing reduced motility and absence of fertilizing potential for α-estrogen receptor and no substantial modifications of male fertility for β-estrogen receptor.
Section snippets
Presence of membrane estrogen receptor in human sperm
The presence of specific binding sites for 17βE2 on human sperm surface has been suggested by several studies (Hernandez-Perez et al., 1979) although the nature of these receptors has not been investigated in these studies. We have recently identified and characterized a receptor for estrogen on human sperm membrane (Luconi et al., 1999) using functional and biochemical approaches similar to those applied by our group to characterize the non-genomic receptor for P on human sperm surface (Luconi
Effects of intracellular calcium concentrations ([Ca2+]i)
Addition of 17βE2 to fura-loaded spermatozoa induced a rapid and sustained rise in [Ca2+]i in a dose-dependent manner. Fig. 2 shows the typical calcium waves observed in response to 17βE2 (panel A) in comparison with the typical wave obtained in response to progesterone (P, panel B), a well known stimulator of calcium increase and acrosome reaction of human spermatozoa (Baldi et al., 1999). The shapes of calcium waves were quite different, indeed, while P induces a first rapid peak followed by
Conclusions
In conclusion, the estrogen receptor detected in human sperm surface is apparently involved in the activation of two different signal transduction pathways, namely an increase of [Ca2+]i and of tyrosine phosphorylation of proteins confirming the findings in other cell types for non-genomic/rapid actions of estrogens (Revelli et al., 1998). The effects of the estrogen result in inhibition of P-stimulated calcium influx and AR. Since both these steroids are present in the follicular fluid (
References (24)
- et al.
Female sex steroid concentrations in the ampullary and isthmic regions of the human fallopian tube and their relationship to plasma concentrations during the menstrual cycle
Am. J. Obstet. Gynecol.
(1980) - et al.
Estrogen-specific target site identified by progesterone-11α-hemisuccinate-(2-[125I]iodohistamine) in mouse brain membranes
J. Steroid. Biochem. Mol. Biol.
(1996) - et al.
Preovulatory follicular fluid steroid levels in stimulated and unstimulated cycles triggered with human chorionic gonadotropin
Fertil. Steril.
(1991) - et al.
Immunochemical studies of estrogen receptors
J. Steroid Biochem.
(1984) - et al.
The selective binding of steroids to human spermatozoa
Contraception
(1977) - et al.
Characterization of membrane estrogen binding proteins from rabbit uterus
Mol. Cell. Endocrinol.
(1999) - et al.
Membrane receptors for steroid hormones: a case for specific cell surface binding sites for vitamin D metabolites and estrogens
Biochem. Biophys. Res. Commun.
(1998) - et al.
Human sperm activation during capacitation and acrosome reaction: role of calcium, protein phosphorylation and lipid remodelling pathways
Front. Biosci.
(1996) - et al.
Non-genomic progesterone receptor on human spermatozoa: biochemical aspects and clinical implications
Steroids
(1999) - et al.
Photoaffinity labeling with progesterone-11α-hemisuccinate-(2-[125I]iodohistamine) identifies four protein bands in mouse brain membranes
J. Neurochem.
(1994)
Progesterone-induced acrosome reaction in stallion spermatozoa is mediated by a plasma membrane progesterone receptor
Biol. Reprod.
Estrogen receptor null mice: what have we learned and where will they lead us?
Endocr. Rev.
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