The Primary Investigation Of The Effects Of GnRH-a On Thermoregulatory Vasomotion In Ovariectomized Rats

Hot flush is one of most common symptoms in perimenopausal women. The pathophysiology of hot flushes remains unknown. A decline in hormone concentrations might lead to alterations in brain neurotransmitters and to instability in the hypothalamic thermoregulatory set point. There are numerous reports of a temporal relationship between luteinizing hormone(LH) secretion and a subsequent flushing response in menopausal women. Because hot flushes occur even after hypophysectomy. it is the gonadotropin releasing hormone(GnRH) that is thought to play a critical role in producing them. The most effective treatments for hot flushes include estrogens and progestagens. Howevert many women are reluctant to accept hormonal treatments for fear of cancer and the existence of hormone replacement therapy contraindication. Women want non-pharmacological treatments but unfortunately such treatments are not very effective, and non-hormonal drugs are often associated with adverse effects. Results from recent studies showed that selective serotonin(5-HT) reuptake inhibitors (SSRIs) and other similar compounds can safely reduce hot flushes. Moreover, the efficacy of these drugs provides new insight into the pathophysiology and treatments of hot flushes. We therefore examined the central effects of gonadotropin releasing hormones analogue(GnRH-a) Alarelin on the thermoregulatory vasomotion in ovariectomized rats and effects of continuous administration of Alarelin on metabolism of 5-HT and parvalbumin (PV) which is a kind of calcium binding protein in CNS of rats were also explored. This may facilitate the search for strategy of coping with hot flushes in non-hormonal drugs.The completely random design was adopted. Ovariectomized rats were anesthetized and mounted in a stereotaxic apparatus for insertion of plastic canula, then GnRH-a was injected into lateral ventricle and the tail skin temperature and rectal temperature were continuously were measured. The effects of Alarelin on tail skin temperatures and rectal temperature responses were assessed in such conditions: direct administration of Alarelin into lateral ventricle, intravenous, at different room temperature, administration of Alarelin following systemic administration of SSRIs Fluoxetine one week. The body weight and concentrations of plasm hormones were measured after three weeks of Alarelin systemic administration. Immunohistochemistry and Image Analysis System were used to evaluate the expression of 5-HT in midbrain nucleus and PV in cortices and Hippocampus in rats.The main findings are as follows:1. Administration of 5ug of the alarelin into the lateral ventricle produced a significantly greater elevation in tail skin temperature and descent in rectal temperature in the castrated rats compared to a negligible change in tail skin temperature or in rectal temperature in the control rats at room temperature (21 degrees ℃); intracerebroventricular administration of saline caused an insignificant change in thermoregulatory responses in the castrated rats and the control rats. In addition, intra cerebral ventricular administration of Alarelin caused an enhancement in cutaneous vasodilation in warmer condition. In contrast, Alarelin hardly caused any cutaneous vasodilation when the temperature was low. Intravenous administration of the same dose of Alarelin was ineffective in producing any temperature effect in castrated rats. All these suggested that the temperature response might be mediated by a central mechanism. After administration of Fluoxetine one week in castrated rats,central administration of Alarelin resulted in a less change in temperature , the reduced change in temperature suggests thatthermoregulatory vasomotion is not only associated with GnRH secretion but also with the neurotransmitter 5-HT.2. The weight of rat and bottom cells in vagina cytology smear were increased after ovariectomy or continuous administration of Alarelin for three weeks. Serum estradiol (E2) LH and follicle stimulating hormone(FSH) concentrat...