Neurobiological Mechanisms of the Onset of Puberty in Primates1
Ei Terasawa and
David L. Fernandez2
Department of Pediatrics (E.T.), Wisconsin Regional
Primate Research Center (E.T., D.L.F.), and Center for Neuroscience
(E.T.), University of Wisconsin-Madison, Madison, Wisconsin
53715-1299
An increase in pulsatile release of LHRH is essential for the
onsetof puberty. However, the mechanism controlling the pubertal
increasein LHRH release is still unclear. In primates the LHRH
neurosecretorysystem is already active during the neonatal period but
subsequentlyenters a dormant state in the juvenile/prepubertal period.
Neithergonadal steroid hormones nor the absence of facilitatory
neuronalinputs to LHRH neurons is responsible for the low levels of
LHRHrelease before the onset of puberty in primates. Recent studies
suggestthat during the prepubertal period an inhibitory neuronal
systemsuppresses LHRH release and that during the subsequent
maturationof the hypothalamus this prepubertal inhibition is removed,
allowingthe adult pattern of pulsatile LHRH release. In fact,
-aminobutyricacid (GABA) appears to be an inhibitory
neurotransmitter responsiblefor restricting LHRH release before the
onset of puberty infemale rhesus monkeys. In addition, it appears that
the reductionin tonic GABA inhibition allows an increase in the
release ofglutamate as well as other neurotransmitters, which
contributesto the increase in pubertal LHRH release. In this review,
developmentalchanges in several neurotransmitter systems controlling
pulsatileLHRH release are extensively reviewed.
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147(3):
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February 1, 2006;
147(2):
1007 - 1013.
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11349 - 11356.
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December 1, 2005;
101(6):
1812 - 1815.
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F. J P Ebling The neuroendocrine timing of puberty
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June 1, 2005;
129(6):
675 - 683.
[Abstract][Full Text][PDF]
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February 8, 2005;
102(6):
2129 - 2134.
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February 1, 2005;
90(2):
1091 - 1099.
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December 1, 2004;
11(4):
725 - 748.
[Abstract][Full Text][PDF]
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December 1, 2004;
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379 - 386.
[Abstract][Full Text][PDF]
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October 1, 2004;
145(10):
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October 1, 2004;
145(10):
4653 - 4659.
[Abstract][Full Text][PDF]
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October 1, 2004;
145(10):
4447 - 4451.
[Abstract][Full Text][PDF]
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September 1, 2004;
71(3):
909 - 918.
[Abstract][Full Text][PDF]
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August 1, 2004;
71(2):
588 - 597.
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June 1, 2004;
25(6):
194 - 200.
[Full Text][PDF]
A. Flor-Cisneros, E. W. Leschek, D. P. Merke, K. M. Barnes, M. Coco, G. B. Cutler Jr., and J. Baron In Boys with Abnormal Developmental Tempo, Maturation of the Skeleton and the Hypothalamic-Pituitary-Gonadal Axis Remains Synchronous
J. Clin. Endocrinol. Metab.,
January 1, 2004;
89(1):
236 - 241.
[Abstract][Full Text][PDF]
T. M. Plant and M. L. Barker-Gibb Neurobiological mechanisms of puberty in higher primates
Hum. Reprod. Update,
January 1, 2004;
10(1):
67 - 77.
[Abstract][Full Text][PDF]
A.-S. Parent, G. Teilmann, A. Juul, N. E. Skakkebaek, J. Toppari, and J.-P. Bourguignon The Timing of Normal Puberty and the Age Limits of Sexual Precocity: Variations around the World, Secular Trends, and Changes after Migration
Endocr. Rev.,
October 1, 2003;
24(5):
668 - 693.
[Abstract][Full Text][PDF]
M. E. Wilson, J. Fisher, K. Chikazawa, R. Yoda, A. Legendre, D. Mook, and K. G. Gould Leptin Administration Increases Nocturnal Concentrations of Luteinizing Hormone and Growth Hormone in Juvenile Female Rhesus Monkeys
J. Clin. Endocrinol. Metab.,
October 1, 2003;
88(10):
4874 - 4883.
[Abstract][Full Text][PDF]
M. M. Lee Reproductive Hormones in Infant Girls--a Harbinger of Adult Reproductive Function?
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August 1, 2003;
88(8):
3513 - 3514.
[Full Text][PDF]
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Endocrinology,
August 1, 2003;
144(8):
3663 - 3676.
[Abstract][Full Text][PDF]
M. S. Golub, C. E. Hogrefe, S. L. Germann, B. L. Lasley, K. Natarajan, and A. F. Tarantal Effects of Exogenous Estrogenic Agents on Pubertal Growth and Reproductive System Maturation in Female Rhesus Monkeys
Toxicol. Sci.,
July 1, 2003;
74(1):
103 - 113.
[Abstract][Full Text][PDF]
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Endocrinology,
June 1, 2003;
144(6):
2566 - 2579.
[Abstract][Full Text][PDF]
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Exp Biol Med,
July 1, 2002;
227(7):
455 - 464.
[Abstract][Full Text][PDF]
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279 - 302.
[Abstract][Full Text][PDF]
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143(4):
1459 - 1466.
[Abstract][Full Text][PDF]
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86(6):
2364 - 2368.
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