201:. This triggers the release of GnRH into the hypophyseal portal capillary bloodstream, where the GnRH hormone activates the pituitary to release luteinizing hormone and follicle stimulating hormone. In addition to classical neurotransmitters, some guidance molecules can change the wiring of GnRH neurons to the portal capillary system, altering the strength of the signal to the pituitary gland.
49:(FSH) into the wider bloodstream. When GnRH neurons change their pattern of release from the juvenile to the adult pattern of GnRH secretion, puberty is initiated. Failure of GnRH neurons to form the proper connections, or failure to successfully stimulate the pituitary with GnRH, means that puberty is not initiated. These disruptions to the GnRH system cause reproductive disorders like
61:
90:
from the nose to the brain, GnRH neurons pass through nasal tissue, the early skull, and move through several regions of the forebrain before reaching their destinations. Along the way, secreted and membrane-bound molecules guide them in the right direction and help to set their movement speed. GnRH
73:
In 1989, two research groups independently discovered that GnRH neurons, which in adults are scattered throughout the hypothalamus, do not originate in this region of the brain. Instead, they migrate into the brain along olfactory axon fibers from the nose. Most GnRH neurons are born from stem cells
1160:
115:
78:
earlier in embryogenesis. This subset of cells migrates into the nasal placode, where they intermix with GnRH neurons born in this region, and migrate together into the brain.
629:
Messina, Andrea; Ferraris, Nicoletta; Wray, Susan; Cagnoni, Gabriella; Donohue, Duncan E.; Casoni, Filippo; Kramer, Phillip R.; Derijck, Alwin A.; Adolfs, Youri (2011-12-15).
74:
in the nasal placode (embryonic nasal tissue). More recently, it was discovered that a subset of GnRH neurons can trace their origins not from the nasal placode, but from the
197:. These neurotransmitters cause electrical activity that is regulated through development to cause broad changes in calcium ion entry into the cell through voltage-sensitive
840:"Suppression of β1-integrin in gonadotropin-releasing hormone cells disrupts migration and axonal extension resulting in severe reproductive alterations"
37:
in the brain that control the release of reproductive hormones from the pituitary. These brain cells control reproduction by secreting GnRH into the
789:"Capture of microtubule plus-ends at the actin cortex promotes axophilic neuronal migration by enhancing microtubule tension in the leading process"
322:"Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode"
631:"Dysregulation of Semaphorin7A/β1-integrin signaling leads to defective GnRH-1 cell migration, abnormal gonadal development and altered fertility"
381:"Neural crest and ectodermal cells intermix in the nasal placode to give rise to GnRH-1 neurons, sensory neurons, and olfactory ensheathing cells"
185:
The shift to high frequency electrical activity in GnRH neurons is the signal that initiates puberty. GnRH neurons receive input from classical
225:
provide the GnRH neurons with information about the body's status to help determine whether reproduction should be prioritized or suppressed.
41:, so are sometimes referred to as "sex neurons". This small capillary network carries GnRH to the anterior pituitary, causing release of
209:
GnRH neurons integrate information from the body to regulate reproduction. The strongest activator of GnRH neurons is a hormone called
1048:"Neuropeptide Y directly inhibits neuronal activity in a subpopulation of gonadotropin-releasing hormone-1 neurons via Y1 receptors"
688:"Hepatocyte growth factor acts as a motogen and guidance signal for gonadotropin hormone-releasing hormone-1 neuronal migration"
479:"Reproduction, smell, and neurodevelopmental disorders: genetic defects in different hypogonadotropic hypogonadal syndromes"
108:
50:
91:
neurons that fail to enter the brain, or that migrate to the wrong brain region, are not functional and can even undergo
46:
112:
478:
582:"Semaphorin 4D regulates gonadotropin hormone-releasing hormone-1 neuronal migration through PlexinB1-Met complex"
165:, which are the molecular filaments that give a cell its shape. This causes contractions in the cell (similar to
38:
123:
64:
Fluorescence image of GnRH neurons (blue) with elements of their cellular cytoskeletons shown in red and green.
242:
Marques, Pedro; Skorupskaite, Karolina; Rozario, Kavitha S.; Anderson, Richard A.; George, Jyothis T. (2000).
134:
Scientists have discovered how guidance molecules cause GnRH neurons to speed up or slow down. Normally, any
194:
143:
938:"Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A"
1000:
333:
278:
34:
1097:"Metabolic influences on reproduction: adiponectin attenuates GnRH neuronal activity in female mice"
989:"Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54"
42:
687:
269:
Schwanzel-Fukuda, M; Pfaff, DW (1989). "Origin of luteinizing hormone-releasing hormone neurons".
302:
166:
135:
1126:
1077:
1028:
969:
918:
869:
820:
769:
720:
668:
650:
611:
562:
513:
459:
410:
361:
294:
96:
54:
1165:
1116:
1108:
1067:
1059:
1018:
1008:
959:
949:
908:
900:
859:
851:
810:
800:
759:
751:
710:
702:
658:
642:
601:
593:
552:
544:
503:
493:
449:
441:
400:
392:
351:
341:
286:
186:
107:
embryonic GnRH neurons, slows movement but helps them to move straight along their pathway.
740:"Calcium release-dependent actin flow in the leading process mediates axophilic migration"
1004:
337:
282:
1121:
1096:
1072:
1047:
964:
937:
913:
888:
864:
839:
815:
788:
764:
739:
715:
663:
630:
606:
581:
557:
532:
508:
454:
429:
405:
380:
214:
104:
87:
1023:
988:
356:
321:
1154:
445:
174:
170:
147:
855:
755:
706:
396:
306:
162:
139:
75:
31:
954:
243:
218:
198:
159:
987:
de Roux, N; Genin, E; Carel, JC; Matsuda, F; Chaussain, JL; Milgrom, E (2003).
430:"From nose to brain: development of gonadotrophin-releasing hormone-1 neurones"
213:. GnRH neurons also integrate information from the body through hormones like
210:
119:
805:
654:
531:
Casoni, F; Hutchins, BI; Donohue, D; Fornaro, M; Condie, BG; Wray, S (2012).
498:
1013:
346:
190:
151:
92:
1130:
1081:
1032:
973:
922:
873:
824:
773:
724:
672:
615:
566:
517:
463:
414:
597:
365:
298:
1112:
1063:
904:
646:
95:. Failure of GnRH neurons to migrate into the brain is the main cause of
60:
889:"The calcium oscillator of GnRH-1 neurons is developmentally regulated"
548:
533:"SDF and GABA interact to regulate axophilic migration of GnRH neurons"
222:
379:
Forni, PE; Taylor-Burds, C; Melvin, VS; Williams, T; Wray, S (2011).
290:
27:
155:
59:
100:
23:
150:
cause the release of these calcium ions back into the cell
118:, accelerating movement speeds. Other guidance cues like
154:, where calcium sensing proteins re-organize the cell's
138:
in the cell are rapidly pulled into organelles like the
1161:Gonadotropin-releasing hormone and gonadotropins
993:Proceedings of the National Academy of Sciences
326:Proceedings of the National Academy of Sciences
244:"Physiology of GnRH and Gonadotropin Secretion"
8:
1095:Klenke, U; Taylor-Burds, C; Wray, S (2014).
126:also regulate the movement of GnRH neurons.
1046:Klenke, U; Constantin, S; Wray, S (2010).
887:Constantin, S; Klenke, U; Wray, S (2010).
1120:
1071:
1022:
1012:
963:
953:
912:
863:
814:
804:
763:
738:Hutchins, BI; Klenke, U; Wray, S (2013).
714:
662:
605:
556:
507:
497:
453:
404:
355:
345:
39:hypophyseal portal capillary bloodstream
234:
320:Wray, S; Grant, P; Gainer, H (1989).
7:
793:Frontiers in Cellular Neuroscience
14:
446:10.1111/j.1365-2826.2010.02034.x
856:10.1523/JNEUROSCI.3057-12.2012
787:Hutchins, BI; Wray, S (2014).
756:10.1523/JNEUROSCI.3758-12.2013
707:10.1523/JNEUROSCI.4979-06.2007
397:10.1523/JNEUROSCI.6087-10.2011
24:gonadotropin-releasing hormone
1:
434:Journal of Neuroendocrinology
51:hypogonadotropic hypogonadism
955:10.1371/journal.pbio.1001808
177:, pulling the cell forward.
47:follicle stimulating hormone
1182:
486:Frontiers in Endocrinology
806:10.3389/fncel.2014.00400
635:Human Molecular Genetics
499:10.3389/fendo.2014.00109
477:Valdes-Socin, H (2014).
1014:10.1073/pnas.1834399100
844:Journal of Neuroscience
744:Journal of Neuroscience
695:Journal of Neuroscience
586:Journal of Cell Biology
537:Journal of Cell Science
385:Journal of Neuroscience
347:10.1073/pnas.86.20.8132
30:, are the cells in the
65:
936:Giacobini, P (2014).
686:Giacobini, P (2007).
598:10.1083/jcb.200806160
580:Giacobini, P (2008).
144:endoplasmic reticulum
93:programmed cell death
63:
1113:10.1210/en.2013-1677
1064:10.1210/en.2009-1198
905:10.1210/en.2010-0118
35:infundibular nucleus
1005:2003PNAS..10010972D
838:Parkash, J (2012).
338:1989PNAS...86.8132W
283:1989Natur.338..161S
167:muscle contractions
43:luteinizing hormone
850:(47): 16992–7002.
647:10.1093/hmg/ddr403
549:10.1242/jcs.101675
148:Guidance molecules
66:
641:(24): 4759–4774.
250:. MDText.com, Inc
187:neurotransmitters
171:adhesive proteins
97:Kallmann Syndrome
55:Kallmann Syndrome
1173:
1135:
1134:
1124:
1092:
1086:
1085:
1075:
1043:
1037:
1036:
1026:
1016:
984:
978:
977:
967:
957:
933:
927:
926:
916:
884:
878:
877:
867:
835:
829:
828:
818:
808:
784:
778:
777:
767:
750:(28): 11361–71.
735:
729:
728:
718:
692:
683:
677:
676:
666:
626:
620:
619:
609:
577:
571:
570:
560:
528:
522:
521:
511:
501:
483:
474:
468:
467:
457:
428:Wray, S (2010).
425:
419:
418:
408:
376:
370:
369:
359:
349:
317:
311:
310:
291:10.1038/338161a0
266:
260:
259:
257:
255:
239:
1181:
1180:
1176:
1175:
1174:
1172:
1171:
1170:
1151:
1150:
1139:
1138:
1094:
1093:
1089:
1045:
1044:
1040:
999:(19): 10972–6.
986:
985:
981:
948:(3): e1001808.
935:
934:
930:
886:
885:
881:
837:
836:
832:
786:
785:
781:
737:
736:
732:
690:
685:
684:
680:
628:
627:
623:
579:
578:
574:
543:(21): 5015–25.
530:
529:
525:
481:
476:
475:
471:
427:
426:
422:
391:(18): 6915–27.
378:
377:
373:
319:
318:
314:
277:(6211): 161–4.
268:
267:
263:
253:
251:
241:
240:
236:
231:
207:
183:
169:) that link to
132:
113:hyperpolarizing
84:
71:
17:
12:
11:
5:
1179:
1177:
1169:
1168:
1163:
1153:
1152:
1149:
1148:
1146:
1144:
1142:
1137:
1136:
1107:(5): 1851–63.
1087:
1058:(6): 2736–46.
1038:
979:
928:
899:(8): 3863–73.
879:
830:
779:
730:
678:
621:
572:
523:
469:
420:
371:
332:(20): 8132–6.
312:
261:
233:
232:
230:
227:
215:neuropeptide Y
206:
203:
182:
179:
131:
128:
83:
82:Cell migration
80:
70:
67:
15:
13:
10:
9:
6:
4:
3:
2:
1178:
1167:
1164:
1162:
1159:
1158:
1156:
1147:
1145:
1143:
1141:
1140:
1132:
1128:
1123:
1118:
1114:
1110:
1106:
1102:
1101:Endocrinology
1098:
1091:
1088:
1083:
1079:
1074:
1069:
1065:
1061:
1057:
1053:
1052:Endocrinology
1049:
1042:
1039:
1034:
1030:
1025:
1020:
1015:
1010:
1006:
1002:
998:
994:
990:
983:
980:
975:
971:
966:
961:
956:
951:
947:
943:
939:
932:
929:
924:
920:
915:
910:
906:
902:
898:
894:
893:Endocrinology
890:
883:
880:
875:
871:
866:
861:
857:
853:
849:
845:
841:
834:
831:
826:
822:
817:
812:
807:
802:
798:
794:
790:
783:
780:
775:
771:
766:
761:
757:
753:
749:
745:
741:
734:
731:
726:
722:
717:
712:
708:
704:
701:(2): 431–45.
700:
696:
689:
682:
679:
674:
670:
665:
660:
656:
652:
648:
644:
640:
636:
632:
625:
622:
617:
613:
608:
603:
599:
595:
592:(3): 555–66.
591:
587:
583:
576:
573:
568:
564:
559:
554:
550:
546:
542:
538:
534:
527:
524:
519:
515:
510:
505:
500:
495:
491:
487:
480:
473:
470:
465:
461:
456:
451:
447:
443:
440:(7): 743–53.
439:
435:
431:
424:
421:
416:
412:
407:
402:
398:
394:
390:
386:
382:
375:
372:
367:
363:
358:
353:
348:
343:
339:
335:
331:
327:
323:
316:
313:
308:
304:
300:
296:
292:
288:
284:
280:
276:
272:
265:
262:
249:
245:
238:
235:
228:
226:
224:
220:
216:
212:
204:
202:
200:
196:
192:
188:
180:
178:
176:
172:
168:
164:
161:
157:
153:
149:
145:
141:
137:
129:
127:
125:
121:
117:
116:GIRK channels
114:
110:
106:
102:
98:
94:
89:
81:
79:
77:
68:
62:
58:
56:
52:
48:
44:
40:
36:
33:
29:
25:
21:
1104:
1100:
1090:
1055:
1051:
1041:
996:
992:
982:
945:
942:PLOS Biology
941:
931:
896:
892:
882:
847:
843:
833:
796:
792:
782:
747:
743:
733:
698:
694:
681:
638:
634:
624:
589:
585:
575:
540:
536:
526:
489:
485:
472:
437:
433:
423:
388:
384:
374:
329:
325:
315:
274:
270:
264:
252:. Retrieved
247:
237:
208:
199:ion channels
184:
175:cell surface
163:cytoskeleton
140:mitochondria
136:calcium ions
133:
85:
76:neural crest
72:
32:hypothalamic
20:GnRH neurons
19:
18:
219:adiponectin
160:microtubule
120:semaphorins
105:depolarizes
26:expressing
1155:Categories
229:References
211:kisspeptin
205:Regulation
181:Physiology
111:activates
655:0964-6906
191:glutamate
152:cytoplasm
88:migration
86:On their
45:(LH) and
16:Cell type
1131:24564393
1082:20351316
1033:12944565
974:24618750
923:20555030
874:23175850
825:25505874
774:23843509
725:17215404
673:21903667
616:18981235
567:22976302
518:25071724
464:20646175
415:21543621
248:Endotext
223:hormones
221:. These
130:Movement
103:, which
1166:Neurons
1122:3990841
1073:2875836
1001:Bibcode
965:3949669
914:2940530
865:5238668
816:4245908
799:: 400.
765:3724331
716:6672060
664:3221532
607:2575794
558:3533389
509:4088923
492:: 109.
455:2919238
406:3101109
366:2682637
334:Bibcode
307:4310861
299:2645530
279:Bibcode
173:on the
69:Origins
28:neurons
1129:
1119:
1080:
1070:
1031:
1024:196911
1021:
972:
962:
921:
911:
872:
862:
823:
813:
772:
762:
723:
713:
671:
661:
653:
614:
604:
565:
555:
516:
506:
462:
452:
413:
403:
364:
357:298229
354:
305:
297:
271:Nature
254:2 July
691:(PDF)
482:(PDF)
303:S2CID
189:like
156:actin
22:, or
1127:PMID
1078:PMID
1029:PMID
970:PMID
919:PMID
870:PMID
821:PMID
770:PMID
721:PMID
669:PMID
651:ISSN
612:PMID
563:PMID
514:PMID
460:PMID
411:PMID
362:PMID
295:PMID
256:2024
217:and
195:GABA
193:and
158:and
122:and
101:GABA
1117:PMC
1109:doi
1105:155
1068:PMC
1060:doi
1056:151
1019:PMC
1009:doi
997:100
960:PMC
950:doi
909:PMC
901:doi
897:151
860:PMC
852:doi
811:PMC
801:doi
760:PMC
752:doi
711:PMC
703:doi
659:PMC
643:doi
602:PMC
594:doi
590:183
553:PMC
545:doi
541:125
504:PMC
494:doi
450:PMC
442:doi
401:PMC
393:doi
352:PMC
342:doi
287:doi
275:338
142:or
124:HGF
109:SDF
53:or
1157::
1125:.
1115:.
1103:.
1099:.
1076:.
1066:.
1054:.
1050:.
1027:.
1017:.
1007:.
995:.
991:.
968:.
958:.
946:12
944:.
940:.
917:.
907:.
895:.
891:.
868:.
858:.
848:32
846:.
842:.
819:.
809:.
795:.
791:.
768:.
758:.
748:33
746:.
742:.
719:.
709:.
699:27
697:.
693:.
667:.
657:.
649:.
639:20
637:.
633:.
610:.
600:.
588:.
584:.
561:.
551:.
539:.
535:.
512:.
502:.
488:.
484:.
458:.
448:.
438:22
436:.
432:.
409:.
399:.
389:31
387:.
383:.
360:.
350:.
340:.
330:86
328:.
324:.
301:.
293:.
285:.
273:.
246:.
146:.
99:.
57:.
1133:.
1111::
1084:.
1062::
1035:.
1011::
1003::
976:.
952::
925:.
903::
876:.
854::
827:.
803::
797:8
776:.
754::
727:.
705::
675:.
645::
618:.
596::
569:.
547::
520:.
496::
490:5
466:.
444::
417:.
395::
368:.
344::
336::
309:.
289::
281::
258:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
