Role of the cAMP signaling pathway in the regulation of gonadotropin-releasing hormone secretion in GT1 cells

被引:69
作者
Vitalis, EA
Costantin, JL
Tsai, PS
Sakakibara, H
Paruthiyil, S
Iiri, T
Martini, JF
Taga, M
Choi, ALH
Charles, AC
Weiner, RI
机构
[1] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, Ctr Reprod Sci, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Sch Med, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
[3] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[4] Yokohama City Univ, Dept Obstet & Gynecol, Yokohama, Kanagawa 2360004, Japan
关键词
D O I
10.1073/pnas.040545197
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We studied the signaling pathways coupling gonadotropin-releasing hormone (GRH) secretion to elevations in cAMP levels in the GT1 GnRH-secreting neuronal cell line. We hypothesized that increased cAMP could be acting directly by means of cyclic nucleotide-gated (CNG) cation channels or indirectly by means of activation of cAMP-dependent protein kinase (PKA), We showed that GT1 cells express the three CNC subunits present in olfactory neurons (CNG2, -4.3, and -5) and exhibit functional cAMP-gated cation channels. Activation of PKA does not appear to be necessary for the stimulation of GnRH release by increased levels of cAMP, In fact, pharmacological inhibition of PKA activity caused an increase in the basal secretion of GnRH, Consistent with this observation activation PKA inhibited adenylyl cyclase activity, presumably by inhibiting adenylyl cyclase V expressed in the cells. Therefore, the stimulation of GnRH release by elevations in cAMP appears to be the result of depolarization of the neurons initiated by increased cation conductance by cAMP-gated cation channels. Activation of PKA may constitute a negative-feedback mechanisms for lowering cAMP levels. We hypothesize that these mechanisms could result in oscillations in cAMP levels, providing a biochemical basis for timing the pulsatile release of GnRH.
引用
收藏
页码:1861 / 1866
页数:6
相关论文
共 42 条
[1]  
ALTSCHUL SF, 1990, J MOL BIOL, V215, P403, DOI 10.1006/jmbi.1990.9999
[2]  
ALVAREZ R, 1995, MOL PHARMACOL, V48, P616
[3]   NEUROPEPTIDE-Y STIMULATES LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE FROM SUPERFUSED HYPOTHALAMIC GT(1)-7 CELLS [J].
BESECKE, LM ;
WOLFE, AM ;
PIERCE, ME ;
TAKAHASHI, JS ;
LEVINE, JE .
ENDOCRINOLOGY, 1994, 135 (04) :1621-1627
[4]  
Bönigk W, 1999, J NEUROSCI, V19, P5332
[5]   HETEROMERIC OLFACTORY CYCLIC NUCLEOTIDE-GATED CHANNELS - A SUBUNIT THAT CONFERS INCREASED SENSITIVITY TO CAMP [J].
BRADLEY, J ;
LI, J ;
DAVIDSON, N ;
LESTER, HA ;
ZINN, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (19) :8890-8894
[6]   MECHANISMS OF SPONTANEOUS CALCIUM OSCILLATIONS AND ACTION-POTENTIALS IN IMMORTALIZED HYPOTHALAMIC (GT1-7) NEURONS [J].
CHARLES, AC ;
HALES, TG .
JOURNAL OF NEUROPHYSIOLOGY, 1995, 73 (01) :56-64
[7]  
CLEGG CH, 1987, J BIOL CHEM, V262, P13111
[8]   Spontaneous action potentials initiate rhythmic intercellular calcium waves in immortalized hypothalamic (GT1-1) neurons [J].
Costantin, JL ;
Charles, AC .
JOURNAL OF NEUROPHYSIOLOGY, 1999, 82 (01) :429-435
[9]   SIGNALING PATHWAYS INVOLVED IN GNRH SECRETION IN GT(1) CELLS [J].
DELAESCALERA, G ;
CHOI, ALH ;
WEINER, RI .
NEUROENDOCRINOLOGY, 1995, 61 (03) :310-317
[10]   GENERATION AND SYNCHRONIZATION OF GONADOTROPIN-RELEASING-HORMONE (GNRH) PULSES - INTRINSIC-PROPERTIES OF THE GT1-1 GNRH NEURONAL CELL-LINE [J].
DELAESCALERA, GM ;
CHOI, ALH ;
WEINER, RI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) :1852-1855