Androgens Increase Gonadotropin-Releasing Hormone Neuron Firing Activity in Females and Interfere with Progesterone Negative Feedback
| Autor: | Justyna Pielecka, Suzanne M. Moenter, Samuel D. Quaynor |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
endocrine system
medicine.medical_specialty Time Factors medicine.drug_class Green Fluorescent Proteins Mice Transgenic Gonadotropin-releasing hormone Biology Models Biological Gonadotropin-Releasing Hormone Mice Endocrinology Negative feedback Internal medicine Extracellular medicine Animals Progesterone gamma-Aminobutyric Acid Feedback Physiological Neurons GnRH Neuron Estradiol Brain Dihydrotestosterone Androgen Electrophysiology medicine.anatomical_structure nervous system Androgens Ovariectomized rat Female Neuron Algorithms hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Endocrinology. 147:1474-1479 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2005-1029 |
| Popis: | GnRH neurons are the central regulators of fertility, and their activity is modulated by steroid feedback. In women with hyperandrogenemic infertility and in animal models of these disorders, elevated androgen levels interfere with progesterone (P) negative feedback. Our previous work showed that steroids altered the frequency and amplitude of γ-aminobutyric acid (GABA) transmission to GnRH neurons. Specifically, P inhibited GABA transmission, which can excite GnRH neurons, whereas dihydrotestosterone (DHT) increased GABA transmission. In this study the GnRH neuron firing rate was examined in the same animal models. Adult (>2 months) female mice were ovariectomized and treated for 8–12 d with implants containing estradiol (E), E and P, E and DHT, or E, P, and DHT. Targeted extracellular recordings were used to examine the long-term firing activity of green fluorescent protein-identified GnRH neurons in brain slices from these mice. In comparing E alone to E plus P animals, P increased the percentage of time that GnRH neurons were quiescent and reduced the area under the curve of the firing rate and the instantaneous firing frequency, suggesting that P provides additional negative feedback over E alone. The addition of DHT markedly increased GnRH neuron activity in both the presence and absence of P. DHT also altered the firing pattern of GnRH neurons, such that peaks in the firing rate detected by the Cluster8 algorithm were approximately doubled in frequency and amplitude. These data support and extend our previous findings and are consistent with the hypothesis that the changes in GABAergic transmission observed in these animal models impact upon the activity of GnRH neurons, and central androgen action probably stimulates GnRH release. |
| Databáze: | OpenAIRE |
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