Nongenomic actions of progesterone on human spermatozoa

Baldi, Elisabetta; Krausz, Csilla; Forti, Gianni

doi:10.1016/1043-2760(95)00083-t

Cited by 35 publications

(23 citation statements)

References 64 publications

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“…So, as our study suggests, MSJ-1 could interact with Hsp70-2 during spermiogenesis in promoting cytomorphogenic events; in spermatozoa this unique DnaJ protein may have other roles, such as involvement during fertilization by interacting with other Hsp70 proteins present in sperm cells [22] to promote the assembly of a protein signaling complex. In this regard, the function of DnaJ proteins in the maturation and activation of steroid hormone receptors has now been well established [6,[38][39][40] and, in addition, the stimulatory actions of progesterone on mammalian spermatozoa have been known for many years [41][42][43]. Work on examining the possible function of MSJ-1 during mouse fertilization and tracking its fate in the fertilized egg is in progress in our laboratory.…”

Section: Discussionmentioning

confidence: 95%

MSJ-1, a Mouse Testis-Specific DnaJ Protein, Is Highly Expressed in Haploid Male Germ Cells and Interacts with the Testis-Specific Heat Shock Protein Hsp70-21

Berruti

Martegani

2001

Biology of Reproduction

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The MSJ-1 gene encodes a murine DnaJ homologue that is expressed specifically in adult testis. DnaJ proteins act as cochaperones of Hsp70 proteins in promoting diverse cellular functions. In this study we used recombinant MSJ-1 proteins to produce MSJ-1 antiserum and to carry out in vitro binding assays. In a wide immunoscreening of mouse tissues, affinity-purified MSJ-1 antibodies recognize a unique protein of 30 kDa in male germ cells only. MSJ-1 is able to interact with the testis-specific Hsp70-2 protein and can be coimmunoprecipitated with Hsp70-2 from spermatogenic cells; binding of these two chaperones is consistent with the presence of a third component, which is so far unknown. MSJ-1 is weakly detected in early round spermatids, and its protein content increases in cytodifferentiating spermatids where it colocalizes with the developing acrosome and their postnuclear region. Hsp70-2, which is known to be highly expressed in meiotic cells, shows a subcellular localization in late differentiating spermatids that overlaps that of MSJ-1. MSJ-1 is also maintained in testicular and epididymal spermatozoa, where it sharply demarcates into two distinct cell areas; the outer surface of the acrosomal vesicle, and the centrosomal area. On the whole, our findings are consistent with a role for MSJ-1 in acrosome formation and centrosome adjustment during spermatid development, whereas its presence in mature spermatozoa suggests a special function during fertilization, shortly afterward, or both.

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Section: Discussionmentioning

confidence: 95%

MSJ-1, a Mouse Testis-Specific DnaJ Protein, Is Highly Expressed in Haploid Male Germ Cells and Interacts with the Testis-Specific Heat Shock Protein Hsp70-21

Berruti

Martegani

2001

Biology of Reproduction

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“…Several other signal transduction pathways have been associated with P 4 's action in non-ovarian tissue. These signal transduction pathways include the suppression of adenylate cyclase, activation of a G protein-linked phosphatidylcholine-specific phospholipase C, induction of diacylglycerol and inositol 1,4,5-triphosphate, stimulation of tyrosine kinase activity, and regulation of chloride channels [2,33,41,42]. The ability of P 4 to activate these pathways in GCs is presently being investigated.…”

Section: Discussionmentioning

confidence: 98%

Progesterone Mediates its Anti-Mitogenic and Anti-Apoptotic Actions in Rat Granulosa Cells Through a Progesterone-Binding Protein With Gamma Aminobutyric AcidA Receptor-Like Features1

Peluso

Pappalardo

1998

Biology of Reproduction

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Progesterone (P4) inhibits small granulosa cell (GC) mitosis and large GC apoptosis. These actions are steroid specific and dose dependent and are inhibited by the progesterone receptor (PR) antagonist, RU-486. However, these cells do not express the nuclear PR but rather an ill-defined P4-binding protein (P4BP). This binding protein could function as a receptor and mediate P4's actions in GCs. Therefore, a series of studies was designed to characterize this P4BP. First, an antibody directed against the ligand-binding site of the nuclear PR was used in a Western blot analysis. This analysis revealed the presence of a 60-kDa P4BP within ovarian and GC lysates as well as within an ovarian membrane preparation. This protein was not observed in lysates of cells derived from the ovarian surface epithelium. In addition, this P4BP was immunoprecipitated by an antibody to the alpha1 chain of the gamma aminobutyric acidA (GABA(A)) receptor, suggesting that the P4BP could be the ovarian GABA(A) receptor. Since activation of the rat ovarian GABA(A) receptor increases intracellular cAMP levels, GCs were cultured with control medium supplemented with either 8-bromo-cAMP (8-br-cAMP), P4, or muscimol (a GABA agonist). Increases in cAMP were detected by monitoring the cAMP-dependent phosphorylation of cAMP response element-binding protein (CREB). Phosphorylated CREB was not observed in control or P4-treated cultures, but it was detected in the majority of both small and large GCs exposed to either 8-br-cAMP or muscimol. Since activation of the GABA(A) receptor with muscimol increases phosphorylated CREB but P4 does not, this study indicates that P4 does not activate the ovarian GABA(A) receptor. However, both bicuculline, a GABA(A) receptor antagonist, and the antibody to PR inhibited P4's ability to prevent both insulin-dependent mitosis and apoptosis. Collectively, these studies suggest that P4 mediates its anti-mitotic and anti-apoptotic effects through this 60-kDa P4BP, which has GABA(A) receptor-like properties and is localized within the surface membrane of GCs.

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“…Signal transduction cascades that are initiated following binding of sperm to ZP3 employ distinct sperm G i proteins as critical transducing elements (29,31,32). On the contrary, discrete signaling steps set in motion by progesterone acting at a plasma membrane receptor are less understood, and a diverse array of molecular mechanisms has been proposed (33). In contrast to stimulation of sperm by ZP, there is currently no evidence for the involvement of G proteins in the progesteroneinduced Ca 2ϩ influx in human sperm (34,35).…”

Section: Discussionmentioning

confidence: 99%

A new prostaglandin E receptor mediates calcium influx and acrosome reaction in human spermatozoa

Schaefer

Hofmann

Schultz

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Zona pellucida protein 3, a protein of the egg's extracellular matrix, and progesterone secreted by granulosa cells surrounding the oocyte are regarded as physiological stimuli of sperm acrosome reaction. Signal transduction steps initiated by both stimuli result in influx of Ca 2؉ from the extracellular space. Herein, we propose a role for prostaglandin (PG) E as a physiological inducer of Ca 2؉ In vivo, ejaculated and epididymal mammalian spermatozoa are not able to fertilize an egg immediately but have to undergo a process of maturation in the female reproductive tract. This time-dependent acquisition of fertilizing capacity called ''capacitation'' is correlated with changes in sperm motility, metabolism, plasma membrane fluidity, and intracellular ion concentrations (1). In capacitated spermatozoa, local stimuli acting in vicinity of the oocyte induce the acrosome reaction (AR), an exocytotic event leading to release of hydrolytic enzymes and substantial reorganization of the sperm plasma membrane (1). To date, two physiological inducers of the AR are known: Subsequent to species-specific binding of sperm to the zona pellucida (ZP), the oocyte's extracellular matrix (2-4), one of the three major proteins forming the mouse ZP, ZP3, elicits the AR (5). Progesterone secreted by ovarian follicular cells surrounding the ovulated egg also initiates the AR (6), and a priming role of the steroid for the induction of the AR by the ZP has been suggested (7).Signal transduction steps in sperm resulting in AR are understood poorly. One of the essential features of the AR is an influx of Ca 2ϩ from the extracellular space required to promote the fusion between the outer acrosomal membrane and the overlying sperm plasma membrane (1). The lack of knowledge on signaling steps leading to Ca 2ϩ influx and AR contrasts with the detailed information about the expression and subcellular localization of classical signal transduction components like G protein-coupled receptors (8), receptor kinases (9), G proteins (10, 11), and effectors such as enzymes (11) and ion channels (12). Thus, the delineation of signaling cascades in sperm is a crucial first step to understand the physiology of fertilization at the molecular level.In the present study, we identified a new role for E prostaglandins as physiological inducers of the AR in humans and provide evidence for the expression of a G protein-coupled E prostanoid (EP) receptor in human sperm. MATERIALS AND METHODSSperm Sample Preparation. Human semen samples were obtained from couples undergoing in vitro fertilization because of female infertility. Sperm samples with normal parameters of sperm count, motility, and morphology were pooled and included in this study. Motile sperm fractions were isolated by a swim-up procedure in hypertonic Biggers Whitten and Whittingham (BWW) medium (for composition, see refs. 13 and 14) supplemented with 10% fetal calf serum (BWW-FCS). Capacitation was promoted by incubating sperm suspensions (0.5-2 ϫ 10 7 per ml) for 6-8 h at 37°C in a humi...

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Nongenomic actions of progesterone on human spermatozoa

Cited by 35 publications

References 64 publications

MSJ-1, a Mouse Testis-Specific DnaJ Protein, Is Highly Expressed in Haploid Male Germ Cells and Interacts with the Testis-Specific Heat Shock Protein Hsp70-21

MSJ-1, a Mouse Testis-Specific DnaJ Protein, Is Highly Expressed in Haploid Male Germ Cells and Interacts with the Testis-Specific Heat Shock Protein Hsp70-21

Progesterone Mediates its Anti-Mitogenic and Anti-Apoptotic Actions in Rat Granulosa Cells Through a Progesterone-Binding Protein With Gamma Aminobutyric AcidA Receptor-Like Features1

A new prostaglandin E receptor mediates calcium influx and acrosome reaction in human spermatozoa

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