scholarly journals Estrogen Differentially Affects Expression of Calcium Handling Genes in Female and Male Adult Cardiomyocytes

2012 ◽  
Vol 1 (3) ◽  
pp. 31-37 ◽  
Author(s):  
Xiaojing Mu ◽  
Pamela Harvey

Premenopausal women have a lower risk of developing heart disease compared with postmenopausal women and age-matched men. However, the debate about whether estrogen is cardioprotective is ongoing due to conflicting results from basic science and clinical trials as well as signaling pathways that make interpretation of effects difficult. Calcium handling in the contracting cells of the heart, the cardiomyocytes, is one of the most important pathways involved in heart function. We sought to determine if calcium-handling genes are regulated by estrogen in a sexually dimorphic manner to explain differences in heart health between men and women.  Cardiomyocytes were isolated from the hearts of healthy male and female rats and were treated with different doses of estrogen (300pM, 10nM). Expression of a set of calcium handling genes was then measured to determine the effect of estrogen. Our results demonstrate that estrogen differentially regulates calcium-handling genes in female and male cells, an effect that is also dose-dependent. To our knowledge, this is the first study to examine expression of this comprehensive set of calcium-handling genes in response to estrogen and to consider its effects separately on cardiomyocytes isolated from males and females.

Author(s):  
Denise Börzsei ◽  
Daniel Priksz ◽  
Renáta Szabó ◽  
Mariann Bombicz ◽  
Zoltán Karácsonyi ◽  
...  

The prevalence of cardiovascular diseases dramatically increases with age, therefore striving to maintain a physiological heart function became particularly important. We aimed to study the voluntary exercise evoked cardioprotective effects in aged male and female rats, from genetic alterations to changes in heart performance. We divided 20-month-old female and male Wistar rats to control and running groups. After the 12-week-long experimental period, echocardiographic measurements were performed. Afterwards, hearts were either removed for biochemical measurements or mounted into a Langendorff-perfusion system to detect infarct size. The following genes and their proteins were analyzed from heart: catechol-O-methyltransferase (Comt), endothelin-1 (Esm1), Purkinje cell protein-4 (Pcp4), and osteoglycin (Ogn). Recreational exercise caused functional improvements; however, changes were more prominent in males. Cardiac expression of Comt and Ogn were reduced as a result of exercise in aged males, while Pcp4 and Esm1 showed a marked overexpression, along with a markedly improved diastolic function. The key result of this study is that exercise enhanced the expression of the Pcp4 gene and protein, a recently described regulator of calcium balance in cardiomyocytes, and suppressed Comt and Ogn gene expression, that has been associated with impaired cardiac function. In addition, as a result of exercise, a significant improvement was observed in the size of infarct elicited by left anterior descending coronary artery occlusion. Our results clearly show that age and sex-dependent changes were both apparent in key proteins linked to cardiovascular physiology. Exercise-moderated fundamental genetic alterations may have contributed to the functional adaptation of the heart.


1999 ◽  
Vol 91 (5) ◽  
pp. 1447-1447 ◽  
Author(s):  
Astrid Chiari ◽  
Joseph R. Tobin ◽  
Hui-Lin Pan ◽  
David D. Hood ◽  
James C. Eisenach

Background Cholinergic agents produce analgesia after systemic and intrathecal administration. A retrospective review showed that intrathecal neostigmine was more potent in women than in men, suggesting a sex difference in this response. The purpose of this study was to determine whether such a sex difference exists in normal rats and to examine the pharmacologic mechanisms that underlie this difference. Methods Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), or RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), or phentolamine alpha-adrenergic antagonist) with antinociception determined to a noxious heat stimulus to the hind paw. Time versus subcutaneous paw temperature relationships were defined for males and females. Results Neostigmine produced dose-dependent antinociception with five times greater potency in female than in male rats. Neostigmine-induced antinociception was reversed in male rats by atropine and unaffected by mecamylamine, whereas it was partially reduced by each antagonist alone in females and completely reversed after injection of both. RJR-2403 was more potent in females than in males, whereas there was no sex difference to bethanechol. Phentolamine partially reversed antinociception from RJR-2403 in females. Paw temperature increased more rapidly in females than in males for the same lamp intensity. Conclusions These data demonstrate a large sex difference in antinociception to intrathecal neostigmine that is primarily the result of a nicotinic component in females. Phentolamine reversal suggests that part of this nicotinic component may rely on spinal norepinephrine release. A better understanding of this sex difference could lead to development of novel pain therapy for women.


Endocrinology ◽  
2015 ◽  
Vol 156 (7) ◽  
pp. 2571-2581 ◽  
Author(s):  
Virginia Mela ◽  
Francisca Díaz ◽  
Ana Belen Lopez-Rodriguez ◽  
María Jesús Vázquez ◽  
Arieh Gertler ◽  
...  

Leptin (Lep) is important in the development of neuroendocrine circuits involved in metabolic control. Because both Lep and metabolism influence pubertal development, we hypothesized that early changes in Lep signaling could also modulate hypothalamic (HT) systems involved in reproduction. We previously demonstrated that a single injection of a Lep antagonist (Antag) on postnatal day (PND)9, coincident with the neonatal Lep peak, induced sexually dimorphic modifications in trophic factors and markers of cell turnover and neuronal maturation in the HT on PND13. Here, our aim was to investigate whether the alterations induced by Lep antagonism persist into puberty. Accordingly, male and female rats were treated with a pegylated super Lep Antag from PND5 to PND9 and killed just before the normal appearance of external signs of puberty (PND33 in females and PND43 in males). There was no effect on body weight, but in males food intake increased, subcutaneous adipose tissue decreased and HT neuropeptide Y and Agouti-related peptide mRNA levels were reduced, with no effect in females. In both sexes, the Antag increased HT mRNA levels of the kisspeptin receptor, G protein-coupled recepter 54 (Gpr54). Expression of the Lep receptor, trophic factors, and glial markers were differently affected in the HT of peripubertal males and females. Lep production in adipose tissue was decreased in Antag-treated rats of both sexes, with production of other cytokines being differentially regulated between sexes. In conclusion, in addition to the long-term effects on metabolism, changes in neonatal Lep levels modifies factors involved in reproduction that could possibly affect sexual maturation.


1984 ◽  
Vol 79 (4) ◽  
pp. 402-412 ◽  
Author(s):  
Th. F. Schaible ◽  
J. Scheuer

1995 ◽  
Vol 268 (4) ◽  
pp. R951-R957 ◽  
Author(s):  
Y. X. Wang ◽  
J. T. Crofton ◽  
H. Liu ◽  
K. Sato ◽  
D. P. Brooks ◽  
...  

To determine which ovarian hormone is involved in the sexually dimorphic antidiuretic action of vasopressin, the antidiuretic response to vasopressin was examined in sham-operated nonestrous female rats chronically treated with vehicle and in ovariectomized rats treated with vehicle, progesterone, estradiol, or the combination of estradiol and progesterone, respectively. Three-week-old female rats were sham operated or ovariectomized, and a slow-release hormone pellet was implanted at the 6th wk. The experiment was performed at the 10th to 12th wk in conscious, chronically instrumented rats hydrated with tap water (2% body wt). Infusion of vasopressin at rates of 10-1,000 pg.min-1.kg body wt-1 resulted in a dose-dependent antidiuretic response that was significantly enhanced in ovariectomized rats compared with the intact nonestrous females. Progesterone had no effect, whereas estradiol attenuated and restored the antidiuretic response to vasopressin to a level similar to that in intact nonestrous female rats. These results suggest that it is estrogen, but not progesterone, that reduces the antidiuretic response to vasopressin in the female rat.


1989 ◽  
Vol 121 (2) ◽  
pp. 343-349 ◽  
Author(s):  
E. Saridaki ◽  
D. A. Carter ◽  
S. L. Lightman

ABSTRACT The role of γ-aminobutyric acid (GABA) in the control of oxytocin and arginine vasopressin (AVP) release from the posterior pituitary was investigated using the GABA agonist muscimol and the GABA antagonists bicuculline and picrotoxin. Two perifusion model systems were studied using (a) intact isolated posterior pituitaries (IPP) and (b) neurosecretosomes from both male and female rats. In experiments on tissue from male rats, the stimulated release of oxytocin and AVP in both models was inhibited by muscimol, an effect which was reversed in the presence of bicuculline. Bicuculline alone increased the release of oxytocin only. Although similar responses to muscimol or bicuculline were seen in neurosecretosomes from female animals, neither agent affected oxytocin and AVP release from the intact IPP. Picrotoxin had a similar effect to bicuculline on oxytocin in isolated posterior pituitaries from male as well as female rats, although at the neurosecretosome level a paradoxical inhibition was observed. These results provide evidence for an endogenous GABA receptor mechanism at the level of the neurosecretory terminals in both male and female rats. The sexually dimorphic IPP response suggests a second more complex mechanism involving either pituicytenerve terminal interactions and/or a secondary role of other neurotransmitters in the GABA regulation of neurohypophysial hormones. Journal of Endocrinology (1989) 121, 343–349


2011 ◽  
Vol 43 (7) ◽  
pp. 346-356 ◽  
Author(s):  
Rachel L. Fogle ◽  
Christopher S. Hollenbeak ◽  
Bruce A. Stanley ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
...  

Long-term ethanol exposure leads to a sexually dimorphic response in both the susceptibility to cardiac pathology (protective effect of the female heart) and the expression of selected myocardial proteins. The purpose of the present study was to use proteomics to examine the effect of chronic alcohol consumption on a broader array of cardiac proteins and how these were affected between the sexes. Male and female rats were maintained for 18 wk on a 40% ethanol-containing diet in which alcohol was provided in drinking water and agar blocks. Differences in the content of specific cardiac proteins in isopycnic centrifugal fractions were determined using mass spectrometry on iTRAQ-labeled tryptic fragments. A random effects model of meta-analysis was developed to combine the results from multiple iTRAQ experiments. Analysis of a network of proteins involved in cardiovascular system development and function showed that troponins were oppositely regulated by alcohol exposure in females (upregulated) vs. males (downregulated), and this effect was validated by Western blot analysis. Pathway analysis also revealed that alcohol-consuming males showed increased expression of proteins involved in various steps of oxidative phosphorylation including complexes I, III, IV, and V, whereas females showed no change or decreased content. One implication from these findings is that females may be protected from the toxic effects of alcohol due to their ability to maintain contractile function, maintain efficiency of force generation, and minimize oxidative stress. However, the alcohol-induced insult may lead to increased production of reactive oxygen species and structural abnormalities in male myocardium.


Sign in / Sign up

Export Citation Format

Share Document