Olfactory receptor (OR)-associated events are mediated by well-conserved components in the olfactory epithelium, including olfactory G-protein (G_olf), adenylate cyclase III (ACIII), and olfactory marker protein (OMP). The expression of ORs has recently been observed in non-olfactory tissues where they are involved in monitoring extracellular chemical cues. The large number of OR genes and their sequence similarities illustrate the need to find an effective and simple way to detect non-olfactory OR-associated events. In addition, expression profiles and physiological functions of ORs in non-olfactory tissues are largely unknown. To overcome limitations associated with using OR as a target protein, this study used OMP with G_olf and ACIII as targets to screen for potential OR-mediated sensing systems in non-olfactory tissues. Here, we show using western blotting, real-time PCR, and single as well as double immunoassays that ORs and OR-associated proteins are co-expressed in diverse tissues. The results of immunohistochemical analyses showed OMP (+) cells in mouse heart and in the following cells using the corresponding marker proteins c-kit, keratin 14, calcitonin, and GFAP in mouse tissues: interstitial cells of Cajal of the bladder, medullary thymic epithelial cells of the thymus, parafollicular cells of the thyroid, and Leydig cells of the testis. The expression of ORs in OMP (+) tissues was analyzed using a refined microarray analysis and validated with RT-PCR and real-time PCR. Three ORs (olfr544, olfr558, and olfr1386) were expressed in the OMP (+) cells of the bladder and thyroid as shown using a co-immunostaining method. Together, these results suggest that OMP is involved in the OR-mediated signal transduction cascade with olfactory canonical signaling components between the nervous and endocrine systems. The results further demonstrate that OMP immunohistochemical analysis is a useful tool for identifying expression of ORs, suggesting OMP expression is an indicator of potential OR-mediated chemoreception in non-olfactory systems.

Resveratrol (3,5,4’-trihydroxystilbene; RSV) is one kind of polyphenolic phytoalexin that has many effects on metabolic diseases. This study aimed to evaluate the protective effect of RSV pretreatment on β-cell. Male Sprague Dawley rats weighing 200-230 g were divided into 4 groups: (1) RSV; (2) streptozotocin (STZ, 70 mg/kg, intraperitoneally); (3) STZ after 7 days pretreatment with RSV; and (4) STZ pretreated with nicotinamide. Fasting glucose concentration was measured and an intraperitoneal glucose tolerance test was performed 72 h after STZ injection to determine the diabetic condition. The pancreas was removed 3, 6, 36, and 48 h after STZ injection. STZ induced diabetes in all rats not given RSV pretreatment, whereas none of the RSV-pretreated rats developed diabetes. Pretreatment with RSV inhibited apoptosis and reduced the activation of caspase-3 and poly(ADP-ribose) polymerase (PARP). However, expression of the total length PARP was not affected by pretreatment. Our findings suggest that RSV protects β-cells from STZ simultaneously with inhibiting the activation of PARP.

Context Sex and age are factors conferring resistance to medical treatment in patients with acromegaly. However, their impact on outcomes of transsphenoidal adenomectomy (TSA) has not been evaluated. Objective The purpose of this study was to analyze age- and sex-related differences concerning surgical outcomes of growth hormone (GH)-secreting pituitary adenomas. Design Retrospective Setting Single-center tertiary hospital Participants Patients with acromegaly (n=463) who underwent TSA between January 2000 and July 2014 Intervention TSA Main outcome Tumor characteristics and surgical outcomes Results Sex differences existed in the baseline insulin-like growth factor-1 levels and the mean tumor size. Overall surgical remission rates were 89.7% and 76.5% in male and female patients, respectively (p<0.001). Total tumor tissue resection was performed in 92.6% and 85.8% of male and female participants, respectively (p=0.021). Premenopausal women had a higher proportion of pituitary adenoma with cavernous sinus invasion than did men aged < 50 years (35.3% vs. 21.7%, p=0.007). In immediate postoperative 75- g oral glucose tolerance test (OGTT) tests, fewer premenopausal women reached <1 ng/dL nadir GH levels than did men aged < 50 years (59.9% vs. 87.7%, p<0.001). Surgical results were similar in both sexes among older patients (≥ 50 years). However, premenopausal women had significantly lower long-term remission rates than did men aged < 50 years (69.3% vs. 88.0%, p<0.001). Conclusion Premenopausal women with acromegaly tend to have larger tumors, more aggressive tumor types, and lower remission rates than do men. However, further studies on the clinical implications are needed.

Context: Reports on the incidence, characteristics, and comorbidity in Asian patients with acromegaly are scarce. Objective: To evaluate the incidence of acromegaly and the risk of comorbidities in East Asia, especially South Korea. Design: This nationwide population-based cohort study using the Korean Health Insurance Review and Assessment claims database evaluated the incidence of acromegaly, initially diagnosed from 2010 to 2013. We identified comorbidities during, before, and 2 years after diagnosis. Acromegaly and control cases (718 and 7180, respectively) were included in the analysis. Setting: A longitudinal case-control study using a nationwide population cohort. Results: The mean annual incidence rate of acromegaly was 3.57 cases per 1 000 000. Malignancies occurred in 61 patients with acromegaly (8.5%) during the study period and thyroid cancer was the most common malignancy (n = 38). In the acromegaly group, the overall risk of malignancy was higher: hazard ratio (HR), 2.82 (95% confidence interval [CI]: 2.12–3.74). Malignancy risk was more pronounced in females, with increased risk from the prediagnosis period that is sustained until the postdiagnosis period. Prevalence of diabetes mellitus (DM) and heart failure increased significantly in acromegalic patients. Over the entire period, DM developed in 51.1% and 57.0% of male and female acromegalic patients, respectively. Mortality risk was higher (HR 1.65, 95%; CI: 1.13–2.41) and statistically significant in females (HR 1.75, 95%; CI: 1.07–2.84). Conclusion: Comorbidities associated with acromegaly differed by sex in Korean subjects. High malignancy and mortality risk should be considered in female patients when managing acromegaly in Korea.