Abstract
Serotonin is a neurotransmitter that alters the hypothalamic-pituitary-adrenal axis. To date, however, the molecular mechanisms underlying die role of serotonin in hormone secretion have remained largely unclear. In this study, we report that serotonin activates phospholipase C (PLC) γ1 in an Src-dependent manner in hypothalamic GT1-7 cells, and that pretreatment with either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazole P, 4-d] pyrimidine, an Src-kinase inhibitor, or U73122, a PLC inhibitor, attenuates the serotonin-induced increase in calcium levels. Also, PLCγ1 binds to c-Src through the Src-homology (SH) 223 domain upon serotonin treatment. Moreover, calcium increase is alleviated in the cells transiently expressing SH223 domain-deleted PLCγ1 or lipase inactive mutant PLC γ1, as compared with cells transfected with wild-type PLC γ1. Furthermore, the inhibition of the activities of either PLC or Src results in a significant diminution of the serotonin-induced release of gonadotropin-releasing hormone (GnRI-1). In addition, the results of our small-interfering RNA experiment confirm that endogenous PLC γ1 is a prerequisite for serotonin-mediated signaling pathways. Taken together, our findings demonstrate that serotonin stimulates the release of GnRH through the Src-PLC γ1 pathway, via the modulation of intracellular calcium levels.
| Original language | English |
|---|---|
| Pages (from-to) | 581-591 |
| Number of pages | 11 |
| Journal | Journal of Endocrinology |
| Volume | 190 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2006 Sep 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Endocrinology
Cite this
Serotonin stimulates GnRH secretion through the c-Src-PLC γ1 pathway in GT1-7 hypothalamic cells. / Kim, Hyeon Soo; Yumkham, Sanatombi; Choi, Jang Hyun; Son, Gi Hoon; Kim, Kyungjin; Ryu, Sung Ho; Suh, Pann Ghill.
In: Journal of Endocrinology, Vol. 190, No. 3, 01.09.2006, p. 581-591.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serotonin stimulates GnRH secretion through the c-Src-PLC γ1 pathway in GT1-7 hypothalamic cells
AU - Kim, Hyeon Soo
AU - Yumkham, Sanatombi
AU - Choi, Jang Hyun
AU - Son, Gi Hoon
AU - Kim, Kyungjin
AU - Ryu, Sung Ho
AU - Suh, Pann Ghill
PY - 2006/9/1
Y1 - 2006/9/1
N2 - Serotonin is a neurotransmitter that alters the hypothalamic-pituitary-adrenal axis. To date, however, the molecular mechanisms underlying die role of serotonin in hormone secretion have remained largely unclear. In this study, we report that serotonin activates phospholipase C (PLC) γ1 in an Src-dependent manner in hypothalamic GT1-7 cells, and that pretreatment with either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazole P, 4-d] pyrimidine, an Src-kinase inhibitor, or U73122, a PLC inhibitor, attenuates the serotonin-induced increase in calcium levels. Also, PLCγ1 binds to c-Src through the Src-homology (SH) 223 domain upon serotonin treatment. Moreover, calcium increase is alleviated in the cells transiently expressing SH223 domain-deleted PLCγ1 or lipase inactive mutant PLC γ1, as compared with cells transfected with wild-type PLC γ1. Furthermore, the inhibition of the activities of either PLC or Src results in a significant diminution of the serotonin-induced release of gonadotropin-releasing hormone (GnRI-1). In addition, the results of our small-interfering RNA experiment confirm that endogenous PLC γ1 is a prerequisite for serotonin-mediated signaling pathways. Taken together, our findings demonstrate that serotonin stimulates the release of GnRH through the Src-PLC γ1 pathway, via the modulation of intracellular calcium levels.
AB - Serotonin is a neurotransmitter that alters the hypothalamic-pituitary-adrenal axis. To date, however, the molecular mechanisms underlying die role of serotonin in hormone secretion have remained largely unclear. In this study, we report that serotonin activates phospholipase C (PLC) γ1 in an Src-dependent manner in hypothalamic GT1-7 cells, and that pretreatment with either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazole P, 4-d] pyrimidine, an Src-kinase inhibitor, or U73122, a PLC inhibitor, attenuates the serotonin-induced increase in calcium levels. Also, PLCγ1 binds to c-Src through the Src-homology (SH) 223 domain upon serotonin treatment. Moreover, calcium increase is alleviated in the cells transiently expressing SH223 domain-deleted PLCγ1 or lipase inactive mutant PLC γ1, as compared with cells transfected with wild-type PLC γ1. Furthermore, the inhibition of the activities of either PLC or Src results in a significant diminution of the serotonin-induced release of gonadotropin-releasing hormone (GnRI-1). In addition, the results of our small-interfering RNA experiment confirm that endogenous PLC γ1 is a prerequisite for serotonin-mediated signaling pathways. Taken together, our findings demonstrate that serotonin stimulates the release of GnRH through the Src-PLC γ1 pathway, via the modulation of intracellular calcium levels.
UR - http://www.scopus.com/inward/record.url?scp=33749847235&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749847235&partnerID=8YFLogxK
U2 - 10.1677/joe.1.06727
DO - 10.1677/joe.1.06727
M3 - Article
C2 - 17003259
AN - SCOPUS:33749847235
VL - 190
SP - 581
EP - 591
JO - Journal of Endocrinology
JF - Journal of Endocrinology
SN - 0022-0795
IS - 3
ER -