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There is a widespread interest in defining factors and mechanisms that stimulate proliferation of pancreatic islet β-cells. Pregnancy is a special period when the pancreatic islet displays a highly reproducible physiological proliferation. However, the molecular mechanism of β-cell proliferation during pregnancy is unclear. Here, we used cDNA expression array to explore gene expression profiles of islet at various stages of pregnancy in rats. Differentially expressed genes related to islet proliferation were screened by bioinformatics methods, and further verified by real-time PCR, RT-PCR, and Western blotting. Compared with control group, expressions of hundreds of genes were changed during pregnancy. The differentially expressed genes related to islet proliferation were mainly distributed in three groups: genes involved in transcription regulator activity, genes involved in apoptosis or tumor, and genes for Wnt signaling pathway. Among these genes, expressions of Nupr1, Atf3, Btg2, β-catenin, and c-Myc mRNA were up-regulated during pregnancy. A prominent expression of Nupr1 and Atf3 protein was observed in islets on day 10.5 of pregnancy, i.e., with earlier time phases than proliferation peak. Moreover, we found that prolactin (PRL) can increase the proliferation of β-cell in vitro, which is accompanied by up-regulation of Atf3 and Nupr1, indicating that they may play a crucial role in PRL-induced pancreatic β-cell growth. In conclusion, our results suggest that the transcription factor Nupr1, Atf3, and Wnt pathway may play an important role in adaptive proliferation of pancreatic islets during pregnancy in rats.

Hypothyroidism is often related with increased blood pressure, yet, gender-specific associations between subclinical hypothyroidism (SCH) and hypertension have not been previously assessed. We conducted a large-scale, cross-sectional study from six districts of Jiangsu Province to investigate the association of SCH and blood pressure in female and male adults. In the studied population, 4725 participants (3034 women and 1691 men) aged 20-60 years were included. The prevalence of hypertension was significantly higher in males as compared to females (37.34% vs. 27.39%, P 0.05), while the prevalence of SCH was much higher in women (9.36% vs. 5.32%, P 0.05). Furthermore, the hypertension rate was significantly higher in female SCH group compared to euthyroid (EUT) group(P 0.05), while no significant differences were observed between the two groups in male participants(P 0.05). After adjusting for age and body mass index (BMI), SCH was an independent predictor for increased SBP (OR = 1.47, 95%CI 1.08-1.99, P = 0.015) and elevated pulse pressure (OR = 1.45, 95%CI 1.05-1.99, P = 0.024) in females, and serum thyroid stimulating hormone (TSH) was significantly higher in female hypertensive group as compared to normotensive group (2.09 vs. 1.92 mIU/l, P = 0.0004). In male participants, SCH was not independently correlated with blood pressure, and no significant difference in TSH levels between hypertensive and normotensive groups was observed (1.74 vs. 1.66 mIU/l, P = 0.12). We concluded that SCH is an independent predictor of increased SBP and pulse pressure in females. Thus, thyroid function may influence blood pressure to a greater extent in females compared to males.

The relationship between subclinical thyroid dysfunction and blood pressure has been controversial and received unsufficient attention. Thus, we performed a cross-sectional study conducted among 6,992 inhabitants from six districts of Jiangsu Province to investigate the association of subclinical thyroid dysfunction with blood pressure in China. The data from 6,583 subjects (4,115 women and 2,468 men) were included and divided into three groups: euthyroidism (n = 5669, 86.11%), subclinical hyperthyroidism (n = 108, 1.65%), and subclinical hypothyroidism (n = 806, 12.24%). In the groups with subclinical hypothyroidism and hyperthyroidism, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were not significantly different from those in the groups with euthyroidism after being adjusted for age, sex, BMI, and smoking status (P0.05). More extensively, the SBP and DBP in the group of subclinical hypothyroidism with lower level of TSH (TSH 4.51-10.00 mIU/l, SCH(1)) were significantly higher than those of participants with euthyroidism (P0.05). Multivariable logistic analysis revealed that subclinical hypothyroidism with lower TSH (TSH 4.51-10.00 mIU/l) was an independent risk factor for increased SBP (OR = 1.28, 95% CI 1.03-1.59, P = 0.028). Similar results could not be found between groups of euthyroid and subclinical hypothyroid with higher level of TSH (TSH10 mIU/l, SCH(2)). Further subdivision of the euthyroid group on the basis of a TSH cut-off of 2.5 mIU/l, revealed still no significant difference in blood pressure after adjustment regardless of whether the TSH levels were in the lower reference (TSH 0.40-2.50 mIU/l, n = 4093) or in the upper reference ranges (TSH 2.51-4.50 mIU/l, n = 1576) (P0.05). We concluded that subclinical thyroid dysfunction was not associated with blood pressure. Neither subclinical hyperthyroidism nor subclinical hypothyroidism independently predicted increased blood pressure.