Converse regulatory functions of estrogen receptor-alpha and -beta subtypes expressed in hypothalamic gonadotropin-releasing hormone neurons.

Estradiol (E(2)) acts as a potent feedback molecule between the ovary and hypothalamic GnRH neurons, and exerts both positive and negative regulatory actions on GnRH synthesis and secretion. However, the extent to which these actions are mediated by estrogen receptors (ERs) expressed in GnRH neurons has been controversial. In this study, Single-cell RT-PCR revealed the expression of both ERalpha and ERbeta isoforms in cultured fetal and adult rat hypothalamic GnRH neurons. Both ERalpha and ERbeta or individual ERs were expressed in 94% of cultured fetal GnRH neurons. In adult female rats at diestrus, 68% of GnRH neurons expressed ERs, followed by 54% in estrus and 19% in proestrus. Expression of individual ERs was found in 24% of adult male GnRH neurons. ERalpha exerted marked G(i)-mediated inhibitory effects on spontaneous action potential (AP) firing, cAMP production, and pulsatile GnRH secretion, indicating its capacity for negative regulation of GnRH neuronal function. In contrast, increased E(2) concentration and ERbeta agonists increase the rate of AP firing, GnRH secretion, and cAMP production, consistent with ERbeta-dependent positive regulation of GnRH secretion. Consonant with the coupling of ERalpha to pertussis toxin-sensitive G(i/o) proteins, E(2) also activates G protein-activated inwardly rectifying potassium channels, decreasing membrane excitability and slowing the firing of spontaneous APs in hypothalamic GnRH neurons. These findings demonstrate that the dual actions of E(2) on GnRH neuronal membrane excitability, cAMP production, and GnRH secretion are mediated by the dose-dependent activation of ERalpha and ERbeta expressed in hypothalamic GnRH neurons

Low-grade appendiceal mucinous neoplasm and endometriosis of the appendix

Abstract Background A distended, mucous-filled appendix is known as an appendiceal mucocele. They are a rare form of an appendiceal mass and develop from both benign and malignant processes. Mucoceles can develop secondarily to an obstruction, such as from a fecalith, scarring or, rarely, endometriosis. Only 12 cases of non-neoplastic appendiceal mucoceles caused by endometriosis have been previously described. The association between neoplastic appendiceal mucoceles in the presence of endometriosis is described for the first time in this report. Case presentation A 57-year-old woman presented with a chief complaint of worsening abdominal pain over the past 3 months. Imaging studies revealed an appendiceal mass. Laparoscopic evaluation confirmed an appendiceal mucocele, and the patient underwent complete appendectomy. No evidence of mucinous or endometrial deposits were present within the abdominal cavity. Pathological diagnosis revealed low-grade appendiceal mucinous neoplasm (LAMN) with evidence of endometriosis within the muscularis propria of the appendix. The patient recovered without complications and her abdominal pain completely resolved. Conclusions Endometriosis of the appendix is a rare manifestation and is most often identified as an incidental finding. Endometriosis leading to an obstructive mucocele of the appendix is an exceedingly rare finding, having only been described 12 times in the medical literature. LAMN in the presence of endometriosis of the appendix is described for the first time in this report. The association between appendiceal neoplasms in the presence of endometriosis requires further research in order to optimize operative treatment