Serotonin, a neurotransmitter involved in the regulation of luteinizing hormone release.

The involvement of serotonin (5-HT) in the regulation of LH secretion is discussed on the basis of experimental and physiological models. The role of 5-HT on low amplitude pulsatile LH release in male rats is not yet clear, in spite of the fact that recent results suggest a weak permissive role. In ovariectomized rats, 5-HT expresses a negative influence on the increased rate of LH release, which is converted into a stimulatory effect by pretreatment of the animals with E2. Moreover, in castrated female rats there is a morning/afternoon oscillatory pattern in 5-HT metabolism of brain areas associated with the control of LH secretion including the hypothalamus. In this area, the fluctuation is modulated by E2 in such a way that the peak of 5-HT neural activity occurs simultaneously with the induced afternoon discharge of LH. On the other hand, P enhances the amplitude of the oscillation of hypothalamic 5-HT metabolism concomitantly with a potentiation of the induced LH surge. This facilitatory role of 5-HT upon phasic LH discharge is also evident in intact female rats. The preovulatory surge of LH is accompanied by an increased hypothalamic and, more precisely, ME 5-HT turnover. Furthermore, 5-HT stimulates in vitro LHRH release from the ME. Serotonergic nuclei located in the brain stem seem to mediate this effect.

Suckling-induced changes of vasoactive intestinal peptide concentrations in hypothalamic areas implicated in the control of prolactin release.

The present study was designed to investigate whether the vasoactive intestinal peptide (VIP) concentration in hypothalamic nuclei, dorsal raphe nucleus (DR) and pituitary lobes of lactating rats changes in physiological situations when prolactin (PRL) secretion is stimulated (suckling) or inhibited (pup separation). In addition VIP levels in blood plasma were determined in both situations. Acute suckling induced changes in VIP concentration only in the rostral part of the anterior hypothalamic (rAHN) and the paraventricular (PVN) nuclei of all the brain areas examined. VIP concentration in the rAHN increased at 5 min from 3.52 +/- 0.30 (mean +/- SEM) to 8.67 +/- 1.91 ng/mg protein (p less than 0.05) but fell to baseline values after 30 min suckling (p less than 0.05; 5 vs. 30 min). Although changes in VIP concentration in the suprachiasmatic nucleus (SCN) did not attain statistical significance, they followed the same trends as the changes of VIP in the rAHN. The opposite pattern of changes was observed in the PVN with a decrease in VIP concentration following 5 min suckling (p less than 0.01). At 30 min the VIP values showed a trend towards 0-min values. Pup removal did not affect VIP concentrations in the rAHN, PVN, SCN, median eminence, supraoptic nucleus and DR. VIP values were not detectable in the arcuate nucleus in any of the experimental situations examined. Lactation increased VIP concentration only in the rAHN and PVN when lactating rats with their pups were compared with virgin female diestrous rats. VIP concentration in the anterior lobe of the pituitary from lactating rats did not change with pup separation or suckling.(ABSTRACT TRUNCATED AT 250 WORDS)

Serotonergic innervation of the rat testis.

The presence of 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. in perchloric extracts of each isolated compartment of the adult rat testis. The testicular capsule, interstitial cells and interstitial fluid contained 5-HT, but 5-HT was not detected in the tubular compartment. In a group of adult rats, one testis was unilaterally denervated, and the contralateral testis used as control. The superior spermatic nerve, arising from the renal plexus, was excised and 1 week after surgery 5-HT content was measured in the capsule and interstitial fluid of both testes. Denervation caused a significant fall (34%) in 5-HT content. These results indicate that at least part of the testicular 5-HT derives from a serotonergic innervation of the gonad.

Dorsal raphe lesion alters the estrous cycle and the preovulatory gonadotropin release.

The purpose of this study was to examine the role that the dorsal raphe (DR)-median eminence (ME) serotonergic projection may have in the proestrous gonadotropin and prolactin (PRL) release. DR electrolytic lesions were performed in cycling rats during the first day of diestrus. The effect of DR lesions after 48-72 h of survival (short-term lesioned animals) or after 35-40 days of survival (long-term lesioned animals) on estrous cyclicity, preovulatory gonadotropin and PRL releasing pattern, ovulation and serotonin (5-HT) content of the ME were studied. Following DR lesions the estrous cycle became irregular, remaining in the diestrus phase for several days. Preovulatory gonadotropin release in short-term lesioned animals was increased; on the contrary, in long-term lesioned rats a delay in the surge of these two hormones and a decrease in LH secretion were detected. Long-term lesioned animals also showed a diminished secretion of PRL. The number of ova did not differ between control and lesioned animals. DR lesions in both short- and long-term lesioned rats reduced 5-HT levels in the ME by about 50% and nullified the normal 5-HT decline during the afternoon of proestrus. Our results suggest that the DR exerts a stimulatory influence on the preovulatory gonadotropin release by means of its 5-HT projection to the ME. As the pattern of hormonal secretion in lesioned animals remains similar to that of controls, it may be suggested that this pathway acts as a fine modulator of the mechanisms involved in the regulation of LH and FSH release in cycling rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Dorsal raphe serotonergic projection to the retina. A combined peroxidase tracing-neurochemical/high-performance liquid chromatography study in the rat.

The existence of retinopetal neurons in the rat was verified using a morphological and neurochemical approach. Horseradish peroxidase injected into the posterior chamber of the eye labeled polygonal, ovoid, fusiform and small multipolar neurons in the lateral cell groups of the dorsal raphe nucleus. Very small electrolytic lesions of this region produced after several days of survival a significant decrease in the serotonin content of the retina. These results demonstrate the existence of a centrifugal projection to the retina from the lateral cell groups of the dorsal raphe nucleus and show its probable serotonergic nature. Besides, they also provide a new possibility to explain the presence of serotonin in the retina.

Serotonin stimulates gonadotrophin release by acting directly on the median eminence.

The study examined the effect of serotonin (5-HT) on gonadotrophin release and its tissue site of action using a sequential double chamber perifusion system. Cycling female rats were killed between 12.00 and 13.00 h on the day of proestrus. Median eminences and anterior pituitaries were removed and transferred to perifusion chambers. Two types of experiments were performed: a) five median eminences (ME) were placed in the first chamber and one anterior pituitary in the second chamber. b) In the second group, only the anterior pituitary was perifused. The effluent from the first chamber perifused the second chamber. The effluent from the second chamber was collected for hormone assays. Addition of serotonin (final concentration 0.06, 0.6 and 6.0 uM) stimulated the release of LH and FSH into the perifusion fluid draining the pituitary in series with the median eminences. Pretreatment with the 5-HT receptor blocker cyproheptadine (1 uM) completely inhibited the stimulatory effect of 5-HT. Serotonin was ineffective in stimulating gonadotrophin release when injected into the tube connecting the first and the second chambers (50 ul of 0.6 uM solution) or when the anterior pituitary was perifused alone. Serotonin did not affect the prolactin release in any of the experimental conditions studied. These observations demonstrate that serotonin stimulated the gonadotrophin release by acting on serotoninergic receptors at the level of the median eminence.

Serotonin stimulates gonadotrophin release by acting directly on the median eminence.

The study examined the effect of serotonin (5-HT) on gonadotrophin release and its tissue site of action using a sequential double chamber perifusion system. Cycling female rats were killed between 12.00 and 13.00 h on the day of proestrus. Median eminences and anterior pituitaries were removed and transferred to perifusion chambers. Two types of experiments were performed: a) five median eminences (ME) were placed in the first chamber and one anterior pituitary in the second chamber. b) In the second group, only the anterior pituitary was perifused. The effluent from the first chamber perifused the second chamber. The effluent from the second chamber was collected for hormone assays. Addition of serotonin (final concentration 0.06, 0.6 and 6.0 uM) stimulated the release of LH and FSH into the perifusion fluid draining the pituitary in series with the median eminences. Pretreatment with the 5-HT receptor blocker cyproheptadine (1 uM) completely inhibited the stimulatory effect of 5-HT. Serotonin was ineffective in stimulating gonadotrophin release when injected into the tube connecting the first and the second chambers (50 ul of 0.6 uM solution) or when the anterior pituitary was perifused alone. Serotonin did not affect the prolactin release in any of the experimental conditions studied. These observations demonstrate that serotonin stimulated the gonadotrophin release by acting on serotoninergic receptors at the level of the median eminence.