Non-genomic effects of progestins—inhibition of cell growth and increased intracellular levels of cyclic nucleotides

Sager, Georg; Ørbo, Anne; Jaeger, Ragnhild; Engström, Catharina

doi:10.1016/s0960-0760(02)00269-8

Cited by 29 publications

(13 citation statements)

References 27 publications

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“…However, androgens are clearly required at some level for normal meiotic progression. It has been recently shown that progestins, which like the androgens act through a nuclear hormone receptor, are capable of exerting a non-genomic effect on cell proliferation in the absence of functional progesterone receptor (Sager et al, 2003). Thus, we suggest that androgens may still be required in Sertoli cells for execution of meiosis, but that these hormones are also capable of acting non-genomically, in the absence of AR function, to promote spermatogenesis.…”

Section: Discussionmentioning

confidence: 73%

Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids

2004

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Androgen receptor function is required for male embryonic sexual differentiation, pubertal development and the regulation of spermatogenesis in mammals. During spermatogenesis, this requirement is thought to be mediated by Sertoli cells and its genetic and pharmacological disruption is manifested in spermatocytes as meiotic arrest. Through studies of a hypomorphic and conditional allele of the androgen receptor (Ar) gene, we have uncovered a dual post-meiotic requirement for androgen receptor activity during male germ cell differentiation. Observations in Ar hypomorphic animals demonstrate that terminal differentiation of spermatids and their release from the seminiferous epithelium is AR dependent and maximally sensitive to AR depletion within the testis. Cell-specific disruption of Ar in Sertoli cells of hypomorphic animals further shows that progression of late-round spermatids to elongating steps is sensitive to loss of Sertoli cell AR function, but that progression through meiosis and early-round spermatid differentiation are surprisingly unaffected.

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Section: Discussionmentioning

confidence: 73%

Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids

2004

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“…These PG effects have been reported in a variety of tissues and have been defined as those occurring within 10 min of exposure (3,26). The mechanisms responsible for nongenomic effects of PG are not fully understood.…”

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confidence: 99%

Nongenomic effects of progesterone on the contraction of muscle cells from the guinea pig colon

Xiao¹,

Cao²,

Biancani³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Progesterone (PG) affects muscle cells by genomic mechanisms through nuclear receptors and by nongenomic mechanisms through unidentified pathways. This study aimed to determine the pathways mediating its nongenomic actions. Experiments were performed in dissociated muscle cells from guinea pig colons. Nongenomic actions were defined as those occurring within 10 min of PG exposure. PG blocked the contraction to CCK-8 and NKA (10(-7) M) but did not impair ACh (10(-7) M) and KCl (2.5 x 10(-2) M)-induced contraction. Both CCK-8 and NKA contract muscle cells by releasing calcium from intracellular stores, whereas ACh and KCl can utilize extracellular calcium. PG also blocked the contraction induced by inositol 1,4,5-trisphosphate, thapsigargin, and caffeine, agents that contract muscle cells by releasing calcium from storage sites. The nongenomic actions of PG were transient because they were absent 1 h after the first PG dose, remaining unresponsive after a second PG dose was administered. Furthermore, PG had no effect on the contraction induced by CCK-8 and thapsigargin in muscle cells from animals pretreated with daily intramuscular PG for 4 days. Cytosolic incorporation experiments of [(3)H]PG showed that pretreatment with unlabeled PG significantly reduced the radiolabeled PG incorporation in the cytosol. We conclude that the nongenomic actions of PG on colonic muscle cells transiently blocked calcium release from storage sites, and this response became rapidly desensitized. This effect does not appear to be specific to PG because other steroid hormones such as aldosterone and testosterone can also induce it.

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“…This rapid hormonal effect on Rho kinase II represents mostly non-genomic action of progesterone, as the short incubation time of the hormone would not allow changes in protein expression levels to occur (18, 19). Our expression data negate an effect for short progesterone treatment on Rho kinase II protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…Non-genomic effects of progesterone have been defined as those occurring within 10 min of exposure (18, 19). It has been proposed that progesterone interacts with plasmalemmal receptors and might lead to rapid activation of tyrosine kinases and phospholipases (20), mitogen-activated protein kinase (MAPK) (21), or inhibition of membrane transport systems (22).…”

Section: Introductionmentioning

confidence: 99%

Non-genomic effects of progesterone on Rho kinase II in rat gastric smooth muscle cells

Al‐Shboul

Mustafa

Alhashimi

2013

J. Smooth Muscle Res.

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Various studies have shown that pregnancy is associated with gastrointestinal complaints that might result from disturbance of the normal contractile pattern of smooth muscle. Progesterone is an important steroid hormone, which plays a crucial role in female pregnancy. Progesterone affects muscle cells by genomic mechanisms, through nuclear receptors, and non-genomic mechanisms, through unidentified pathways. Non-genomic actions were defined as those occurring within 10 min of progesterone exposure. The aim of the present study was to investigate the non-genomic effect of progesterone on Rho kinase II activity in gastric smooth muscle. Single smooth muscle cells of the stomach obtained from Sprague Dawley rats were used. Dispersed gastric smooth muscle cells were treated with progesterone or acetylcholine (ACh) separately. Cells designated for progesterone treatment were incubated with 1 μM progesterone for 10 min. Rho kinase II expression and both basal and ACh-induced Rho kinase II activity were measured via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits respectively in both control and progesterone-treated groups. Progesterone inhibited the ACh-induced, but not the basal, Rho kinase II activity in dispersed gastric smooth muscle cells without affecting its expression level. This study suggested that progesterone can rapidly affect the contractile activity of isolated gastric smooth muscle cells in rats via inhibition of the Rho kinase II pathway.

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Non-genomic effects of progestins—inhibition of cell growth and increased intracellular levels of cyclic nucleotides

Cited by 29 publications

References 27 publications

Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids

Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids

Nongenomic effects of progesterone on the contraction of muscle cells from the guinea pig colon

Non-genomic effects of progesterone on Rho kinase II in rat gastric smooth muscle cells

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