ABSTRACT
Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT(1A)) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT(1A) receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT(1A) receptor desensitization. We previously showed that estrogen receptor ß is not necessary for 5-HT(1A) receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT(1A) receptor as measured by hormonal responses to the selective 5-HT(1A) receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT(1A) receptor signaling components including 5-HT(1A) receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT(1A) receptor protein but increased 5-HT(1A) mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT(1A) receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT(1A) receptor signaling pathway and desensitization of 5-HT(1A) receptor signaling.
Subject(s)
Estradiol/pharmacology , Paraventricular Hypothalamic Nucleus/drug effects , Receptor, Serotonin, 5-HT1A/metabolism , Receptors, G-Protein-Coupled/physiology , Animals , Female , Gene Expression/drug effects , HEK293 Cells , Humans , Models, Biological , Paraventricular Hypothalamic Nucleus/metabolism , RNA, Small Interfering/pharmacology , Rats , Rats, Sprague-Dawley , Receptor, Serotonin, 5-HT1A/genetics , Receptor, Serotonin, 5-HT1A/physiology , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/genetics , Signal Transduction/drug effects , Signal Transduction/geneticsABSTRACT
Salary comparisons of male and female ACHE members in 1989 showed that men earned nearly $16,000 more than women. Controlling for race and region, age and experience accounted for most of the explained variation. Women earned significantly more if they had more male mentors, a spouse willing to relocate for their career advancement, or an employer whose policies accommodated families such as flextime and if they themselves socialized informally with other health care executives.
Subject(s)
Health Facility Administrators/economics , Men , Salaries and Fringe Benefits/statistics & numerical data , Women, Working/statistics & numerical data , Age Factors , Family , Female , Humans , Male , Prejudice , Professional Practice Location/economics , Racial Groups , Regression Analysis , Sex Factors , Surveys and Questionnaires , United StatesABSTRACT
This study examines factors contributing to hospital CEOs' voluntary decisions to leave their positions in 1990. Using a longitudinal design, we contrast 49 leavers with 1,362 stayers. We view turnover as influenced by both "push" factors that promote leaving (dissatisfaction with the position) and "hump" factors that need to be overcome (the cost of job change). Push factors giving rise to dissatisfaction include lower compensation, the predecessor's termination, and value incongruity between the CEO and the hospital. Testing the impact of key variables from Fiedler's contingency theory of leadership, we show that task-oriented leaders are relatively less satisfied when compared with relationship-oriented leaders. CEOs also express less satisfaction in low-situational control settings, a measure heavily influenced by perceived inadequate support from medical staff and subordinates. "Hump" factors that deterred leaving included family-related obstacles such as spouse's work or children's school, features mentioned most often by younger CEOs. The study suggests that boards should structure competitively paid positions with opportunities to generate support from the medical staff and subordinates. Recruiters for CEO positions are apprised of the importance of nonwork features in CEOs' willingness to consider new positions.
