Estrogen treatment increases the levels of regulator of G protein signaling-Z1 in the hypothalamic paraventricular nucleus: possible role in desensitization of 5-hydroxytryptamine1A receptors

Carrasco, Gonzalo; Barker, Sheryll A.; Zhang, Y; Damjanoska, Katerina J.; Sullivan, Nicole R.; García, Francisca; D’Souza, Deborah N.; Muma, Nancy A.; Kar, Louis D. Van de

doi:10.1016/j.neuroscience.2004.05.031

Cited by 45 publications

(30 citation statements)

References 30 publications

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“…The RGSRz proteins contain several potential N-and O-linked glycosylation sites, as well as consensus sites for serine, threonine, and tyrosine phosphorylation (De Vries et al, 1995; Center for Biological Sequence Analysis). RGSZ2-related protein moieties of distinct sizes were detected in immunoblots of synaptosomal membranes, as is the case for RGSZ1 and GAIP (Carrasco et al, 2004;Garzón et al, 2004). With the exception of the 24 kDa moiety, these RGSZ2 forms were purified in the glycosylated pool of neural membrane proteins and following treatment with glycosidases, their apparent molecular weight decreased.…”

Section: Discussionmentioning

confidence: 91%

The RGSZ2 Protein Exists in a Complex with μ-Opioid Receptors and Regulates the Desensitizing Capacity of Gz Proteins

Garzón

Rodríguez-Muñoz

López-Fando

et al. 2005

Neuropsychopharmacol

104

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The regulator of G-protein signaling RGS17(Z2) is a member of the RGS-Rz subfamily of GTPase-activating proteins (GAP) that efficiently deactivate GazGTP subunits. We have found that in the central nervous system (CNS), the levels of RGSZ2 mRNA and protein are elevated in the hypothalamus, midbrain, and pons-medulla, and that RGSZ2 is glycosylated in synaptosomal membranes isolated from CNS tissue. In analyzing the function of RGSZ2 in the CNS, we found that when the expression of RGSZ2 was impaired, the antinociceptive response to morphine and [D-Ala 2 , N-MePhe 4 , Gly-ol 5 ]-enkephalin (DAMGO) augmented. This potentiation involved m-opioid receptors and increased tolerance to further doses of these agonists administered 24 h later. High doses of morphine promoted agonist desensitization even within the analgesia time-course, a phenomenon that appears to be related to the great capacity of morphine to activate Gz proteins. In contrast, the knockdown of RGSZ2 proteins did not affect the activity of d receptor agonists, [D-Pen 2,5 ]-enkephalin (DPDPE), and [D-Ala 2 ] deltorphin II. In membranes from periaqueductal gray matter (PAG), both RGSZ2 and the related RGS20(Z1) co-precipitated with m-opioid receptors. While a morphine challenge reduced the association of Gi/o/z with m receptors, it increased their association with the RGSZ2 and RGSZ1 proteins. However, only Gaz subunits co-precipitated with RGSZ2. Doses of morphine that produced acute tolerance maintained the association of Ga subunits with RGSZ proteins even after the analgesic effects had ceased. These results indicate that both RGSZ1 and RGSZ2 proteins influence m receptor signaling by sequestering Ga subunits, therefore behaving as effector antagonists.

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Section: Discussionmentioning

confidence: 91%

The RGSZ2 Protein Exists in a Complex with μ-Opioid Receptors and Regulates the Desensitizing Capacity of Gz Proteins

Garzón

Rodríguez-Muñoz

López-Fando

et al. 2005

Neuropsychopharmacol

104

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“…The 5HT1A receptor is the major inhibitory serotonin receptor, but 5HT1A mRNA expression is not robust in the PVN of macaques and 5HT1A binding is decreased and/or desensitized by E treatment (Gundlah et al, 1999;Lu and Bethea, 2002;Carrasco et al, 2004). 5HT2A and 5HT2C receptors are prominent in the PVN, but they are stimulatory (Gundlah et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Bethea

Centeno

2007

Neuropsychopharmacol

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Corticotropin-releasing hormone (CRH) gene and protein expression were examined in the paraventricular nucleus (PVN) of ovariectomized female macaques treated with placebo or hormone therapy (HT) consisting of either estrogen (E) for 28 days, or progesterone (P) for the last 14 of 28 days, or E for 28 days supplemented with P for the last 14 of 28 days using Silastic capsules implanted s.c. in the periscapular region (n ¼ 4/group). Perfusion fixed sections (25 mm) at five levels of the PVN (rostral to caudal at 250 mm intervals) were immunostained (ICC) with an antibody to human CRH or processed in an in situ hybridization (ISH) assay with a monkey specific CRH riboprobe. The immunostained CRH-positive area was quantified with a Marianas Stereology Workstation and Slidebook 4.2. There was a significant decrease in the immunological CRH signal with E, P, and E + P treatment as measured by total or average pixels and microns (analysis of variance (ANOVA), po0.002; Student-Newman-Keul's post hoc test versus placebo control group, po0.05). There was also a decrease in the number of detectable CRH neurons (ANOVA, po0.03) with HT. The sections processed for ISH were exposed to autoradiographic films. The CRH mRNA signal was analyzed with NIH Image. The average optical density and positive pixel area of the CRH mRNA signal was significantly suppressed by ovarian HT (ANOVA po0.002; StudentNewman-Keul's post hoc test versus placebo control group, po0.05). In summary, 1 month of stable treatment with a moderate dose of E, P or E + P significantly reduced CRH mRNA and protein in the PVN of ovariectomized monkeys. These results suggest that this hormone treatment regimen may increase stress resilience in surgically menopausal primates.

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“…20,21 Studies investigating the relationship between 5-HT and sexual hormones have shown that oestradiol was reported to induce a desensitization of the 5-HT 1A receptors. 22,23 Both estrone and oestradiol are increased in obese men compared with control subjects, a finding attributed to increased peripheral aromatization of androgens. 24 In our study, we found that premature ejaculators were leaner than healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Insight on pathogenesis of lifelong premature ejaculation: inverse relationship between lifelong premature ejaculation and obesity

Gökçe

Ekmekçioğlu

2010

Int J Impot Res

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Although both biological and psychological factors are important in the etiology, the exact pathogenesis of lifelong premature ejaculation (PE) remains to be clarified. Obesity is a worldwide epidemic that contributes to many chronic diseases. Obesity is associated with erectile dysfunction, but the relationship between obesity and PE has not yet been specifically investigated. The aim of this study was to evaluate the relationships of these two conditions. Between January 2008 and December 2009, we evaluated consecutive patients with lifelong PE in the urology outpatient clinic. Control cases without lifelong PE were selected randomly among cases attending the department of internal medicine for a checkup procedure. The age and sex of control group were matched with that of the study group. Body mass index (BMI) of each case was calculated using the World Health Organization criteria by the measurements of the physician instead of relying on verbal expressions. The mean (±s.d.) age of the premature ejaculators was 31.7±5.7 (range 21-51) years and in the control cases it was 32.3±6.7 (range 22-54) years. The comparison of the mean (±s.d.) weight between the study (74.1 ± 11.2 kg) and control groups (81.9 ± 6.4 kg) revealed a significant difference (Po0.001). The mean BMI of premature ejaculators (24.9 ± 3.4 kg m -2 ) was lower than the mean BMI of control (27.5±3.6 kg m -2 ; Po0.001). As the BMI increased, the number of patients decreased in the PE group. The number of the obese cases in the control group (n ¼ 26, 24.1%) was three times greater than the obese premature ejaculators (Po0.005), and the number of PE patients were approximately two times greater than the control cases in the normal-weight class (Po0.001). This is the first prospective study that investigated the relationship between lifelong PE and obesity, and we found that patients with lifelong PE were leaner than the healthy control cases.

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Estrogen treatment increases the levels of regulator of G protein signaling-Z1 in the hypothalamic paraventricular nucleus: possible role in desensitization of 5-hydroxytryptamine1A receptors

Cited by 45 publications

References 30 publications

The RGSZ2 Protein Exists in a Complex with μ-Opioid Receptors and Regulates the Desensitizing Capacity of Gz Proteins

The RGSZ2 Protein Exists in a Complex with μ-Opioid Receptors and Regulates the Desensitizing Capacity of Gz Proteins

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Insight on pathogenesis of lifelong premature ejaculation: inverse relationship between lifelong premature ejaculation and obesity

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