Adipose Tissue Steroid Receptor RNA Activator 1 (SRA1) Expression Is Associated with Obesity, Insulin Resistance, and Inflammation

Steroid receptor RNA activator 1 (SRA1) is involved in pathophysiological responses of adipose tissue (AT) in obesity. In vitro and animal studies have elucidated its role in meta-inflammation. Since SRA1 AT expression in obesity/type 2 diabetes (T2D) and the relationship with immune-metabolic signatures remains unclear, we assessed AT SRA1 expression and its association with immune–metabolic markers in individuals with obesity/T2D. For this, 55 non-diabetic and 53 T2D individuals classified as normal weight (NW; lean), overweight, and obese were recruited and fasting blood and subcutaneous fat biopsy samples were collected. Plasma metabolic markers were assessed using commercial kits and AT expression of SRA1 and selected immune markers using RT-qPCR. SRA1 expression was significantly higher in non-diabetic obese compared with NW individuals. SRA1 expression associated with BMI, PBF, serum insulin, and HOMA-IR in the total study population and people without diabetes. SRA1 associated with waist circumference in people without diabetes and NW participants, whereas it associated inversely with HbA1c in overweight participants. In most study subgroups AT SRA1 expression associated directly with CXCL9, CXCL10, CXCL11, TNF-α, TGF-β, IL2RA, and IL18, but inversely with CCL19 and CCR2. TGF-β/IL18 independently predicted the SRA1 expression in people without diabetes and in the total study population, while TNF-α/IL-2RA predicted SRA1 only in people with diabetes. TNF-α also predicted SRA1 in both NW and obese people regardless of the diabetes status. In conclusion, AT SRA1 expression is elevated in people with obesity which associates with typical immunometabolic markers of obesity/T2D, implying that SRA1 may have potential as a biomarker of metabolic derangements.

Steroidogenic Enzyme and Steroid Receptor Expression in the Equine Accessory Sex Glands

The expression pattern and distribution of sex steroid receptors and steroidogenic enzymes during development of the equine accessory sex glands has not previously been described. We hypothesized that equine steroidogenic enzyme and sex steroid receptor expression is dependent on reproductive status. Accessory sex glands were harvested from mature stallions, pre-pubertal colts, geldings, and fetuses. Expression of mRNA for estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), androgen receptor (AR), 3β-Hydroxysteroid dehydrogenase/Δ5-4 isomerase (3βHSD), P450,17α hydroxylase, 17–20 lyase (CYP17), and aromatase (CYP19) were quantified by RT-PCR, and protein localization of AR, ER-α, ER-β, and 3βHSD were investigated by immunohistochemistry. Expression of AR, ESR2, CYP17, or CYP19 in the ampulla was not different across reproductive statuses (p > 0.1), while expression of ESR1 was higher in the ampulla of geldings and fetuses than those of stallions or colts (p < 0.05). AR, ESR1 and ESR2 expression were decreased in stallion vesicular glands compared to the fetus or gelding, while AR, ESR1, and CYP17 expression were decreased in the bulbourethral glands compared to other glands. ESR1 expression was increased in the prostate compared to the bulbourethral glands, and no differences were seen with CYP19 or 3β-HSD. In conclusion, sex steroid receptors are expressed in all equine male accessory sex glands in all stages of life, while the steroidogenic enzymes were weakly and variably expressed.

Steroid Receptor Coactivator 3 Regulates Synaptic Plasticity and Hippocampus-dependent Memory

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) – a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3+/− mice, hippocampus-dependent functions such as short-term memory and spatial memory were impaired. We further demonstrated that the deficient learning and memory in Src3+/− mice was strongly associated with the impairment of long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses. Mechanistic studies indicated that Src3+/− mutation altered the composition of N-methyl-D-aspartate receptor subunits in the postsynaptic densities of hippocampal neurons. Finally, we showed that SRC3 regulated synaptic plasticity and learning mainly dependent on its lysine acetyltransferase activity. Taken together, these results reveal previously unknown functions of SRC3 in the hippocampus and thus may provide insight into how steroid hormones regulate brain function.