Abstract
Stress exerts profound inhibitory effects on reproductive function by suppression of the pulsatile release of GnRH and therefore LH. Besides the corticotrophin-releasing factor (CRF), this effect also might be mediated via GABAergic signaling within the arcuate nucleus (ARC) since its inhibitory effects on LH pulses and increased activity during stress. In the present study, we investigated the role of endogenous GABAergic signaling within the ARC in stress-induced suppression of LH pulses. Ovariectomised oestradiol-replaced rats were implanted with bilateral and unilateral cannulae targeting toward the ARC and lateral cerebral ventricle respectively. Blood samples (25 μl) were taken via chronically implanted cardiac catheters every 5 min for 6 h for measurement of LH pulses. Intra-ARC infusion of GABAA receptor antagonist, bicuculline (0.2 pmol in 200 nl artificial cerebrospinal fluid (aCSF) each side, three times at 20-min intervals) markedly attenuated the inhibitory effect of lipopolysaccharide (LPS; 25 μg/kg i.v.) but not restraint (1 h) stress on pulsatile LH secretion. In contrast, restraint but not LPS stress-induced suppression of LH pulse frequency was reversed by intra-ARC administration of GABABR antagonist, CGP-35348 (1.5 nmol in 200 nl aCSF each side, three times at 20-min intervals). Moreover, intra-ARC application of either bicuculline or CGP-35348 attenuated the inhibitory effect of CRF (1 nmol in 4 μl aCSF, i.c.v.) on the LH pulses. These data indicate a pivotal and differential role of endogenous GABAA and GABAB signaling mechanisms in the ARC with respect to mediating immunological and psychological stress-induced suppression of the GnRH pulse generator respectively.
Original language | English |
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Pages (from-to) | 9-19 |
Number of pages | 11 |
Journal | Journal of Molecular Endocrinology |
Volume | 55 |
Issue number | 1 |
Early online date | 21 May 2015 |
DOIs | |
Publication status | Published - Aug 2015 |
Keywords
- Animals
- Arcuate Nucleus of Hypothalamus
- Bicuculline
- Cerebellar Nuclei
- Corticotropin-Releasing Hormone
- Estradiol
- Female
- Gonadotropin-Releasing Hormone
- Luteinizing Hormone
- Organophosphorus Compounds
- Pulse
- Rats
- Receptors, GABA
- Stress, Physiological
- gamma-Aminobutyric Acid