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

Abstract

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.

Interactions of Corticotropin-Releasing Factor, Urocortin and Citalopram in a Primate Model of Stress-Induced Amenorrhea

“…Previous studies have also demonstrated that serotonin innervates CRF neurons in the hypothalamus [48,49], and newer data indicate that serotonin decreases CRF [50,51], perhaps via inhibitory interneurons [52]. Therefore, we hypothesized that S-citalopram increased extracellular serotonin, which decreased CRF production and delivery to extrahypothalamic regions including the dorsal raphe.…”

Effects of citalopram on serotonin and CRF systems in the midbrain of primates with differences in stress sensitivity

“…Moreover, CRF regulates serotonin release (Summers et al, 2003, Thomas et al, 2003, Clark et al, 2007, Forster et al, 2008). Previous studies demonstrated that serotonin innervates CRF neurons in the hypothalamus (Phelix et al, 1992, Saphier et al, 1994) and newer data indicate that serotonin decreases CRF (Stout et al, 2002, Lowry et al, 2009), perhaps via inhibitory interneurons (Bethea and Centeno, 2008). Therefore, we hypothesized that citalopram increased extracellular serotonin, which decreased CRF production and delivery to extrahypothalamic regions, including the dorsal raphe.…”

Effect of injectable medroxyprogesterone acetate and etonogestrel implants on GABA-A and serotonin receptors in white and gray matter of the brain: experimental study in rats

“…Caspase 3 is assumed to be the apoptotic effector caspase that is responsible for much of biological apoptosis [37][38][39][40]. Bethea & Centeno suggested that hormone therapy may act globally in the caspase-dependent pathway by decreasing the synthesis of pro-caspase [41]. The results did not provide compelling evidence for a global action of hormone therapy on the caspase-dependent pathway [42].…”