Search Results

You are looking at 1 - 4 of 4 items for

  • Author: Zhao He x
Clear All Modify Search
Free access

Chengyuan Lin, Xue Jiang, Mulan He, Ling Zhao, Tao Huang, Zhaoxiang Bian and Anderson O L Wong

In mammals, pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic hormone with diverse functions but its role in prolactin (PRL) regulation is highly controversial. To shed light on Prl regulation by PACAP in fish model, grass carp pituitary cells was used as a model to examine the receptor specificity and signal transduction for PACAP modulation of prl gene expression in the carp pituitary. Using RT-PCR, PACAP-selective PAC1 receptor was detected in carp lactotrophs. In carp pituitary cells, nanomolar doses of PACAP, but not VIP, could elevate Prl secretion and protein production with concurrent rise in prl mRNA and these stimulatory effects were blocked by PACAP antagonist but not VIP antagonist. PACAP-induced prl mRNA expression could be mimicked by activating adenylate cyclase (AC), increasing cAMP level by cAMP analog, or increasing intracellular Ca2+ ([Ca2+]i) by Ca2+ ionophore/voltage-sensitive Ca2+ channel (VSCC) activator. PACAP-induced prl gene expression, however, was attenuated/abolished by suppressing cAMP production, inhibiting PKA activity, blocking [Ca2+]i mobilization and VSCC activation, calmodulin (CaM) antagonism, and inactivation of JNK and CaM Kinase II (CaMK-II). Similar sensitivity to CaM, JNK, and CaMK-II blockade was also noted by substituting cAMP analog for PACAP as the stimulant for prl mRNA expression. These results, as a whole, provide evidence for the first time that (i) PACAP activation of PAC1 receptor expressed in carp lactotrophs could induce Prl synthesis and secretion, and (ii) Prl production induced by PACAP was mediated by upregulation of prl gene expression, presumably via functional coupling of cAMP/PKA-, Ca2+/CaM-, and MAPK-dependent cascades.

Open access

Huali Yu, Ye Guo, Yang Zhao, Feng Zhou, Kehan Zhao, Mayuqing Li, Junxiong Wen, Zixuan He, Xiaojuan Zhu and Xiaoxiao He

Glucocorticoids (GCs) are a class of steroid hormones that regulate numerous physiological events in the human body. Clinically, glucocorticoids are used for anti-inflammatory and immunosuppressive actions via binding with glucocorticoid receptors (GRs). Emerging evidence has also indicated that inappropriate GC and GR levels are detrimental for brain development and eventually lead to severe neurological diseases. However, the roles of GC/GR signaling in brain development are not fully understood. Here, we showed that stable GR expression levels were critical for brain development, because both GR knockdown and overexpression severely impaired neuronal migration. Further studies showed that the multipolar–bipolar transition and leading process development were interrupted in GR-knockdown and GR-overexpressing neurons. To elucidate the underlying mechanism, we screened the protein levels of downstream molecules and identified RhoA as a factor negatively regulated by the GR. Restoration of the RhoA protein level partially rescued the neuronal migration defects in the GR-knockdown and GR-overexpressing neurons, indicating that RhoA played a major role in GR-mediated neuronal migration. These data suggest that an appropriate level of GC/GR signaling is essential for precise control of neuronal migration.

Free access

Shibin Ding, Ying Fan, Nana Zhao, Huiqin Yang, Xiaolei Ye, Dongliang He, Xin Jin, Jian Liu, Chong Tian, Hongyu Li, Shunqing Xu and Chenjiang Ying

Epidemiological findings on the association between bisphenol A (BPA, 2,2-bis-(4-hydroxyphenyl)propane) exposure and type 2 diabetes mellitus (T2DM) are paradoxical. In animal studies, BPA has been shown to disrupt pancreatic function and blood glucose homeostasis even at a reference ‘safe’ level during perinatal period. In this study, we explored the effects of long-term paternal exposure to a ‘safe’ level of BPA on parents themselves and their offspring. Adult male genitor rats fed with either standard chow diet (STD) or high-fat diet (HFD) were treated respectively with either vehicle or BPA (50 μg/kg per day) for 35 weeks. The male rats treated with vehicle or BPA for 21 weeks were then used as sires, and the adult female rats were fed with STD during the gestation and lactation. Offspring rats were weaned on postnatal day 21 and fed with STD in later life. Metabolic parameters were recorded on the adult male rats and their adult offspring. BPA exposure disrupted glucose homeostasis and pancreatic function, and HFD aggravated these adverse effects. However, BPA exposure did not alter body weight, body fat percentage, or serum lipid. In addition, the paternal BPA exposure did not cause adverse reproductive consequence or metabolic disorder in the adult offspring. Our findings indicate that chronic exposure to a predicted ‘safe’ dose of BPA contributes to glucose metabolic disorders, and that HFD aggravates these adverse effects in paternal rats.

Restricted access

Sisi Luan, Wenkai Bi, Shulong Shi, Li Peng, Zhanbin Li, Jie Jiang, Ling Gao, Yifeng Du, Xu Hou, Zhao He and Jiajun Zhao

Subclinical hyperthyroidism, a condition characterized by decreased thyroid-stimulating hormone (TSH) and normal concentration of thyroid hormone, is associated with an elevated risk for cognitive impairment. TSH is the major endogenous ligand of the TSH receptor (TSHR) and its role is dependent on signal transduction of TSHR. It has not, however, been established whether TSHR signaling is involved in the regulation of cognition. Here, we utilized Tshr knockout mice and found that Tshr deletion led to significantly compromised performance in learning and memory tests. Reduced dendritic spine density and excitatory synaptic density as well as altered synaptic structure in CA1 subfield of the hippocampus were also noted. Furthermore, the synapse-related gene expression was altered in the hippocampus of Tshr -/- mice. These findings suggest that TSHR signaling deficiency impairs spatial learning and memory, which discloses a novel role of TSHR signaling in brain function.