Opposite-sex housing reactivates the declining GnRH system in aged transgenic male mice with FGF signaling deficiency
| Autor: | Pei-San Tsai, Wilson C. J. Chung, Johanna R. Rochester, Tyrone B. Hayes |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Aging Heterozygote endocrine system medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Transgene Fibroblast Growth Factor 3 Hypothalamus Cell Count Mice Transgenic Nerve Tissue Proteins Gonadotropin-releasing hormone Neurotransmission Biology Fibroblast growth factor Synaptic Transmission Gonadotropin-Releasing Hormone Mice Sexual Behavior Animal Physiology (medical) Internal medicine Testis medicine Animals Receptor Fibroblast Growth Factor Type 3 Receptor Mice Knockout Neurons Heterozygote advantage Articles Endocrinology Nerve Degeneration Receptors LHRH hormones hormone substitutes and hormone antagonists Signal Transduction Hormone |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 303:E1428-E1439 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00289.2012 |
| Popis: | The continued presence of gonadotropin-releasing hormone (GnRH) neurons is required for a healthy reproductive lifespan, but factors that maintain postnatal GnRH neurons have not been identified. To begin to understand these factors, we investigated whether 1) fibroblast growth factor (FGF) signaling and 2) interactions with the opposite sex are involved in the maintenance of the postnatal GnRH system. A transgenic mouse model (dnFGFR mouse) with the targeted expression of a dominant-negative FGF receptor (dnFGFR) in GnRH neurons was used to examine the consequence of FGF signaling deficiency on postnatal GnRH neurons. Male dnFGFR mice suffered a significant loss of postnatal GnRH neurons within the first 100 days of life. Interestingly, this loss was reversed after cohabitation with female, but not male, mice for 300–550 days. Along with a rescue in GnRH neuron numbers, opposite-sex housing in dnFGFR males also increased hypothalamic GnRH peptide levels, promoted a more mature GnRH neuronal morphology, facilitated litter production, and enhanced testicular morphology. Last, mice hypomorphic for FGFR3 exhibited a similar pattern of postnatal GnRH neuronal loss as dnFGFR males, suggesting FGF signaling acts, in part, through FGFR3 to enhance the maintenance of the postnatal GnRH system. In summary, we have shown that FGF signaling is required for the continued presence of postnatal GnRH neurons. However, this requirement is not absolute, since sexual interactions can compensate for defects in FGFR signaling, thereby rescuing the declining GnRH system. This suggests the postnatal GnRH system is highly plastic and capable of responding to environmental stimuli throughout adult life. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|