GONADOTROPIN-RELEASING HORMONE SYSTEM DURING PUBERTAL TRANSITION OF FIBROBLAST GROWTH FACTOR 8-DEFICIENT MICE
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1
University of Colorado at Boulder, Department of Integrative Physiology, United States
Gonadotropin-releasing hormone (GnRH) is critical for the onset and maintenance of reproduction in vertebrates. Puberty, a significant transition in life involving reproductive onset, is triggered by increasing levels of GnRH synthesis and secretion. The development of GnRH neurons is highly dependent on fibroblast growth factor (Fgf) signaling. In transgenic mice deficient in Fgf8 signaling (Fgf8 hypomorphs), the genesis of GnRH neurons is disrupted, leading to a 50% decrease in the number of postnatal GnRH neurons. However, the initiation of pubertal onset appears unaffected in these mice, suggesting the presence of compensatory mechanisms. In this study, we sought to understand the nature of these compensatory mechanisms by examining GnRH neuron number and hypothalamic GnRH content in Fgf8 hypomorphs and wildtype (WT) mice within ages encompassing pubertal transition (postnatal day (PN) 10, 20, 25, 30, 35, to 40). Our results showed that GnRH neuron numbers were significantly reduced in Fgf8 hypomorphs compared to WT in all age groups examined. In parallel, significant decreases in hypothalamic GnRH content in Fgf8 hypomorphs were observed in all age groups except PN35. Interestingly, during the pubertal transition at PN35, the GnRH content of Fgf8 hypomorphs increased to a level no longer different from that seen in WT mice. These data indicate that, during puberty, the GnRH system compensates for the loss of GnRH neurons by increasing its overall GnRH production. This speaks to the extraordinary ability of an organism's pubertal drive to overcome pre-existing deficiencies in order to ensure its reproductive onset.
Acknowledgements
This research was supported by NIH 042634 to PST.
References
[1] Chung WC, Moyle SS, Tsai PS. 2008. Fibroblast growth factor 8 signaling through fibroblast growth factor receptor 1 is required for the emergence of gonadotropin-releasing hormone neurons. Endocrinology. 149(10):4997-5003.
[2] Meyers EN, Lewandoski M, and Martin GR. 1998. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat. Genet.18: 136–141.
Keywords:
Fgf8,
GnRH,
Puberty
Conference:
NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology, Ann Arbor, United States, 13 Jul - 16 Jul, 2011.
Presentation Type:
Poster
Topic:
Neuroendocrine control of reproduction
Citation:
Zhang
W,
Rochester
JR,
Kavanaugh
SI and
Tsai
P
(2011). GONADOTROPIN-RELEASING HORMONE SYSTEM DURING PUBERTAL TRANSITION OF FIBROBLAST GROWTH FACTOR 8-DEFICIENT MICE.
Front. Endocrinol.
Conference Abstract:
NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology.
doi: 10.3389/conf.fendo.2011.04.00055
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Received:
18 Jul 2011;
Published Online:
09 Aug 2011.
*
Correspondence:
Ms. Wei Zhang, University of Colorado at Boulder, Department of Integrative Physiology, Boulder, CO, 80309, United States, vevian.zhang@gmail.com