Dorsal Raphe Lesion Alters the Estrous Cycle and the Preovulatory Gonadotropin Release

Abstract

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 provulatory 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. Our results also indicate that the DR plays a role in the release of PRL on proestrus.

Central Orexin A Has Site-Specific Effects on Luteinizing Hormone Release in Female Rats

“…an inhibitory effect on LH release (39,40), whereas the dopaminergic incertohypothalamic tract with terminals in the ZI and POA is stimulatory (3,4,41,42). Similarly, the serotonergic tract originating in the median raphe and innervating the mediobasal hypothalamus is inhibitory (43), whereas the serotonergic tract from the dorsal raphe passing to the POA is stimulatory (44,45), albeit only in the presence of steroids (35). The dual effect of orexin noted here and by others (5,14,19) indicates that this peptide joins the ranks of many other neurotransmitters in modulating GnRH activity bidirectionally.…”

Differential Involvement of 5-Hydroxytryptamine (5HT) in Specific Hypothalamic Areas in the Mediation of Steroid-Induced Changes in Gonadotrophin Release and Sexual Behaviour in Female Rats

“…Others have suggested that the dual effect of 5HT is due to its exerting opposite effects at different sites. Recent evidence based on changes in 5HT turnover indi cates that the POA and ME are sites for the stimulatory action of 5HT on LH release [6,22,25,48,50] while it is inhibitory to both gonadotrophin release and sexual behaviour in the ARC [9,12] and the VMN [10,21,22], Alternatively, these dual effects may reflect the activation of different 5HT recep tors. Indeed, there is some evidence that 5HT is inhibitory to female sexual behaviour via 5HT| receptors and stimulatory via 5HT: receptors [2,32,33,55].…”

“…The rise in 5HT activity seen by Vitale et ai. [48] in the evening hours on the day of proestrus in intact rats may well be associated with the increase in sexual receptivity known to occur at this time [14] rather than the LH surge and explains the relatively small effect seen on the release of the preovulatory LH surge after depletion of 5HT in the ME [50], (b) In the VMN, P, but not oestrogen, reduces 5HT activity at the same time as stimulating receptivity and LH release. This inverse relationship indicates that 5HT is involved in an inhib itory control of both functions as suggested by others [10,22], (c) Both oestrogen and progesterone may stimulate sexual behaviour by reducing 5HT activity in the ARC.…”

Leptin Uptake by Serotonergic Neurones of the Dorsal Raphe

“…Microinjection of serotonin into the dorsal raphe induces feeding in rats (15) and raphe neurones are innervated by dense fibre projections from orexin/hypocretin neurones of the lateral hypothalamus which are implicated in the regulation of food intake (16–18). Beyond metabolism regulation, raphe neurones are also involved in endocrine regulation, including gonadotrophin secretion (19, 20) and the control of sleep patterns (21) and higher cognitive functions (22), all of which are affected by the metabolic state and, consequently leptin, as well (18, 23–25). In fact, leptin receptors are expressed in cells of the raphe nuclei (4–6), including those cells that express the serotonin transporter (26), suggesting that serotonergic neurones of the raphe nuclei may be direct targets of leptin.…”