The hypothalamic control of gonadotrophin secretion is exerted through the pulsatile release of luteinizing hormone-releasing hormone (LHRH), which in turn is regulated by many neurotransmitters and neuropeptides such as noradrenaline, endogenous opioids, gamma-aminobutyric acid, nitric oxide, galanin, excitatory amino acids (through ionotropic receptors such as N-methyl-D-aspartic acid (NMDA) or kainate (KA) receptors) and serotonin. Given that physiological interactions between different neurotransmitters involved in the control of LHRH/LH secretion have been described, the objective of the present experiments was to analyse the effects of activation of different 5-hydroxytryptamine (5-HT) receptor subtypes on gonadotrophin secretion and their role in the NMDA-stimulated LH release.
We analysed gonadotrophin secretion after manipulation of the serotoninergic and aminoacidergic systems and their interaction in 5-, 16- and 23-day-old male and female rats. The animals were decapitated 15 min after the last injection and blood samples were collected. To this end, serum LH and follicle-stimulating hormone (FSH) concentrations were measured in rats treated with 5-hydroxytryptophan methyl ester (a precursor of 5-HT synthesis) plus fluoxetine (a blocker of 5-HT reuptake), D,L–p-chlorophenylalanine methyl ester (a blocker of 5-HT synthesis), R (+)-8-hydroxy-propylaminotetralin hydrobromide (8-OH-DPAT, an agonist of 5-HT1A receptors), (±)2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and α-methyl-5-hydroxytryptamine (agonists of 5-HT2 receptors), and 1-phenylbiguanide (an agonist of 5-HT3 receptors). In addition, the effects of 8-OH-DPAT and DOI on NMDA-stimulated LH secretion were analysed.
Neither the activation nor the blockade of the serotoninergic system modified LH (0.1 ng ml-1) secretion. Basal gonadotropin secretion remained unchanged in 23-day-old male and female rats after selective activation of 5-HT1A, 5-HT2 and 5-HT3 receptors. The stimulatory effect of NMDA on LH secretion was blocked in both sexes after activation of the serotoninergic system, through specific 5-HT1A and 5-HT2 receptors agonists.
Although basal LH secretion is not under the control of the serotoninergic system in prepubertal male and female rats, the specific activation of 5-HT1A and 5-HT2 receptors decreased the stimulatory effect of NMDA on LH secretion.
This work was supported by grant BFI2000-0419-C03.