Estrogens and Gastroparesis: A Clinical Relevance

Rao, Jaladanki N.

doi:10.1007/s10620-013-2683-0

Cited by 15 publications

(14 citation statements)

References 19 publications

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“…Healthy women have also been identified to have slower gastric emptying of solids compared with men (2). This may explain why gastroparesis -a chronic stomach motility disorder in which there is a delayed gastric emptying of food without mechanical obstruction -is more common in women than men (3,4). Furthermore, previous studies assessing colonic motility have demonstrated faster colon transit (shorter transit time) in men compared with women (5-7).…”

Section: Introductionmentioning

confidence: 99%

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Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

et al. 2018

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Abstract. Evidence of sex-related differences in gastrointestinal (GI) functions has been reported in the literature. In addition, various GI disorders have disproportionate prevalence between the sexes. An essential step in the initiation of smooth muscle contraction is the phosphorylation of the 20-kDa regulatory myosin light chain (MLC 20 ) by the Ca 2+ /calmodulin-dependent myosin light chain kinase (MLCK). However, whether male stomach smooth muscle inherits different contractile signaling mechanisms for the regulation of MLC 20 phosphorylation from that in females has not been established. The present study was designed to investigate sex-associated differences in the regulation of MLC 20 phosphorylation and thus muscle contraction in gastric smooth muscle cells (GSMCs). Experiments were performed on GSMCs freshly isolated from male and female rats. Contraction of the GSMCs in response to acetylcholine (ACh), a muscarinic agonist, was measured via scanning micrometry in the presence or absence of the MLCK inhibitor, ML-7. Additionally, the protein levels of MLC 20 , MLCK and phosphorylated MLC 20 were measured by ELISA. The protein levels of MLC 20 and MLCK were indifferent between the sexes. ACh induced greater contraction (P<0.05) as well as greater MLC 20 phosphorylation (P<0.05) in male GSMCs compared with female. Pretreatment of GSMCs with ML-7 significantly reduced the ACh-induced contraction (P<0.05) and MLC 20 phosphorylation (P<0.05) in the male and female cells, and notably, abolished the contractile differences between the sexes. In conclusion, MLC 20 phosphorylation and thus muscle contraction may be activated to a greater extent in male rat stomach compared with that in females. IntroductionIt has been established in previous research that gastrointestinal (GI) motility function is affected by gender (1). Healthy women have also been identified to have slower gastric emptying of solids compared with men (2). This may explain why gastroparesis -a chronic stomach motility disorder in which there is a delayed gastric emptying of food without mechanical obstruction -is more common in women than men (3,4). Furthermore, previous studies assessing colonic motility have demonstrated faster colon transit (shorter transit time) in men compared with women (5-7). In one study, women exhibited less pressure activity in the colon, particularly in the transverse/descending colon, than men (8). Sex-associated differences were also evident in the anal sphincter contraction and anorectal motility (9). For instance, Sun and Read (10) identified that healthy men had stronger anal sphincter pressures compared with women. In the gallbladder, women have been observed to have a slower emptying rate than men under normal conditions, and this may explain the increased probability of gallstone development in women compared with men (11). Sex-dependent differences in esophageal motility in terms of duration and velocity of esophageal contraction have also been also reported (12).In addition, sex-associated differences h...

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Section: Introductionmentioning

confidence: 99%

“…Studies on sex differences in GI motility disorders have generally focused on sex hormone/receptor-mediated effects on tract function (3,17). However, these sex differences may also be associated with alterations in the signaling mechanisms of smooth muscle contractile machinery.…”

Section: Introductionmentioning

confidence: 99%

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

et al. 2018

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“…These disturbances may vary during a female's lifetime due to the varying levels of sex hormones during the menstrual cycle, pregnancy and menopause (5,6). In addition, females have an increased probability of being affected by gastroparesis, a chronic gastric motility disorder, in which gastric emptying of solids and liquids is delayed in the absence of obstruction (7). Although the pathogenesis of the disease remains to be fully elucidated, the importance of estrogen in the regulation of gastric motility in females is evident (8).…”

Section: Introductionmentioning

confidence: 99%

Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect

et al. 2018

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Various gastrointestinal (GI) disorders have a higher prevalence in women than in men. In addition, estrogen has been demonstrated to have an inhibitory effect on the contractility of GI smooth muscle. Although increased plasma estrogen levels have been implicated in GI disorders, the role of gastric estrogen receptor (ER) in these sex-specific differences remains to be fully elucidated. The present study was designed to investigate the sex-associated differences in the expression of the two ER isoforms, ERα and ERβ, and the effect of estrogen on gastric muscle contraction via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. Experiments were performed on single gastric smooth muscle cells (GSMCs) isolated from male and female Sprague Dawley rats. The effect of acetylcholine (ACh), a muscarinic agonist, on the contraction of GSMCs was measured via scanning micrometry in the presence or absence of 1 µM 17β-estradiol (E2), an agonist to the majority of ERs, 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), an ERα agonist, or diarylpropionitrile (DPN), an ERβ agonist. The protein expression levels of ER subtypes in GSMCs were measured using a specifically designed ELISA. GSMCs from female rats had a higher expression of ERα and ERβ protein compared with GSMCs from males. ACh induced less contraction in female that in male GSMCs. Pre-treatment of GSMCs with E2 reduced the contraction of GSMCs from both sexes, but to a greater extent in those from females. PPT and DPN inhibited ACh-induced contraction in GSMCs from females. Furthermore, E2 increased NO and cGMP levels in GSMCs from males and females; however, higher levels were measured in females. Of note, pre-incubation of female GSMCs with Nω-nitro-L-arginine, a NO synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a guanylyl cyclase inhibitor, reduced the inhibitory effect of estrogen on GSMC contraction. In conclusion, estrogen relaxes GSMCs via an NO/cGMP-dependent mechanism, and the reduced contraction in GSMCs from females by estrogen may be associated with the sex-associated increased expression of ERα and ERβ, and greater production of NO and cGMP, compared with that in GSMCs from males.

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“…Emerging evidence strongly indicate that women and female rodents are likely to experience more severe disease manifestations of gastroparesis compared to males [3,4]. In fact, women during their reproductive ages, tend to be disproportionately affected by gastroparesis because their stomach motility is slower to begin with, likely due to elevated levels of sex steroid hormones and nitric oxide [5,6].…”

Section: Introductionmentioning

confidence: 99%

Role of Sex Hormones And Their Receptors On Gastric Nrf2 And Neuronal Nitric Oxide Synthase Function In An Experimental Hyperglycemia Model

Sprouse

Sampath

Gangula

2020

Preprint

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Background: Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim: The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods: Gastric neuromuscular sections from adult female C57BL/6J mice were incubated in normoglycemic (NG, 5mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 hours. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results: Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p<0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions: Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

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Estrogens and Gastroparesis: A Clinical Relevance

Cited by 15 publications

References 19 publications

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect

Role of Sex Hormones And Their Receptors On Gastric Nrf2 And Neuronal Nitric Oxide Synthase Function In An Experimental Hyperglycemia Model

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