Serotonergic Mediation of a Negative Feedback Effect of Estrogen on Luteinizing Hormone Release in Ovariectomized Rats*

Johnson, James H.; Kitts, C S

doi:10.1210/endo-123-5-2270

Cited by 16 publications

(9 citation statements)

References 30 publications

(29 reference statements)

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“…These results, although based on a reduced number of ewes, suggest the existence of some stimulatory influence of serotonin, acting in part through 5HT2 recep tors on LH secretion during this transitory step. The involvement of 5HT2 receptors in both positive and nega tive feedbacks of steroid control of LH secretion has also been suggested in rats [59,60].…”

Section: Distribution the Distribution Of [ 'H]ketanserin Bind Ing Smentioning

confidence: 99%

Differences in Ketanserin Binding in the Ventromedial Hypothalamus of Ewes Responsive or Refractory to Short Days

Corre

Ségu²,

Caldani³

et al. 1994

Neuroendocrinology

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Participation of central 5HT receptors in the inhibition of LH pulsatility during refractoriness to short days (SD) in ewes has been suggested by previous in vivo studies using various 5HT-antagonist such as ketanserin. In the present study, binding of [³H]ketanserin in ewe brain sections was similar to that described in the brain of other species and could correspond with an interaction at 5HT2 receptors sites. Rosenthal analysis from the caudate nucleus was linear (Kd = 3 nM). The displacement studies from the cortex slices showed that the 5HT antagonists such as methysergide, ketanserin, cyproheptadine and spiperone competed with the labelled ligand at nanomolar concentrations whereas serotonin was less active. However, the first 3 drugs recognized different populations of binding sites. Prazosin, an α₁-adrenergic antagonist was inactive, but a slight inhibition of [³H]ketanserin binding was induced by pyrilamine, an H₁ histaminic antagonist, within a nanomolar range. Methysergide (10^–6M), which does not bind to H₁ receptors, was therefore used to determine the nonspecific binding. Quantitative analysis of the binding of 3 nM [³H]ketanserin on sections of the ewe brain at the preopticohypothalamic level was then carried out by autoradiography. The highest binding densities were observed in the caudate nuclei (64.0 fmol/mg tissue Eq) and the mammillary bodies (52.7 fmol/mg tissue Eq) whereas intermediate or low densities were found in the other structures. The anatomical distribution of the labelling was similar to that described in other species for 5HT₂ receptors. Ketanserin binding in these areas was compared between two groups of ovariectomized estradiol-treated Ile-de-France ewes, submitted to artificial short days (SD: 8L: 16D), one group with a high LH pulsatility (responsive to SD) and the other one with a low LH pulsatility (photorefractory to SD). Binding densities were similar for each one of the studied regions between the two groups, except in the ventrolateral part of the mediobasal hypothalamus, where ewes exhibiting high LH pulsatility had a more than 2-fold higher binding density than those with a low LH pulsatility (mean ± SEM, 14.6 ± 1.4 vs. 5.7 ± 1.0 fmol/mg tissue Eq, respectively; p < 0.0016). These results suggest that [³H]ketanserin binding sites in the ventromedial part of the mediobasal hypothalamus could be associated to the regulation of the photoperiodic inhibition of LH at the time of establishment of refractoriness to short days in the Ile-de-France ewe.

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Section: Distribution the Distribution Of [ 'H]ketanserin Bind Ing Smentioning

confidence: 99%

Differences in Ketanserin Binding in the Ventromedial Hypothalamus of Ewes Responsive or Refractory to Short Days

Corre

Ségu²,

Caldani³

et al. 1994

Neuroendocrinology

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“…Regarding the functional role of 5HT2 A receptors, in ovariectomized rats, they seem to be involved in the negative feedback of oestrogens on LH release [49] and in the triggering of LH surge by oestradiol [50]. As previously exposed, it was shown in ewes, that the use of specific antagonists of 5HT2 A receptors liberates the inhibition of pulsatile LHRH/LH activity during refractoriness to short days [18,19].…”

Section: Discussionmentioning

confidence: 99%

Changes in the 5-HT2Areceptor system in the pre-mammillary hypothalamus of the ewe are related to regulation of LH pulsatile secretion by an endogenous circannual rhythm

et al. 2003

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Background: We wanted to determine if changes in the expression of serotonin 2A receptor (5HT2 A receptor) gene in the premammillary hypothalamus are associated with changes in reproductive neuroendocrine status. Thus, we compared 2 groups of ovariectomized-estradioltreated ewes that expressed high vs low LH pulsatility in two different paradigms (2 groups per paradigm): (a) refractoriness (low LH secretion) or not (high LH secretion) to short days in pinealintact Ile-de-France ewes (RSD) and (b) endogenous circannual rhythm (ECR) in free-running pinealectomized Suffolk ewes in the active or inactive stage of their reproductive rhythm.

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“…Manipulation of 5-HT activity in intact and steroid-primed ovariectomised rats also indicates an inhibitory effect. Thus, destruction of 5-HT nerve terminals by 5,7-dehydroxytryptamine (5,7-DHT) in the MBH raises LH levels [36], while systemic administration of 5-hydroxytryptophan (5-HTP), 5-HT uptake inhibitors, and intracerebral injections of 5-HT itself inhibit LH release and their effects can be reversed by antagonists [38, 39, 40, 41, 42]. Based on the use of selective antagonists in some of these experiments it has been suggested that the inhibitory effects are mediated by 5-HT2 receptors [42].…”

Section: Discussionmentioning

confidence: 99%

Serotonin Inhibits Luteinizing Hormone Release via 5-HT1A Receptors in the Zona incerta of Ovariectomised, Anaesthetised Rats Primed with Steroids

Siddiqui

Kotecha²,

Salicioni³

et al. 2000

Neuroendocrinology

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The zona incerta (ZI), an area in the dorsal hypothalamus, contains neuronal systems that appear to control gonadotropin release. Previous findings show that there is an inverse relationship between serotonin (5-HT) activity in the ZI and plasma luteinizing hormone (LH) levels, indicating that the 5-HT system in this area has an inhibitory effect on LH release. Employing anaesthetised, ovariectomised rats primed with 5 µg oestradiol benzoate followed at 48 h by 0.5 mg progesterone, we have shown that 2 µg/side 5-HT in the ZI inhibits the LH surge that normally occurs 4 h after the progesterone treatment. This effect was mimicked by 2 µg/side 8-OH-DPAT, a 5-HT1A agonist, but not by DOI, a 5-HT2 agonist, BMY7378, a presynaptic 5-HT1A agonist or MCPP, a 2B & 2C agonist. The inhibitory effect of 5-HT and 8-OH-DPAT was prevented by pretreatment, 1 h before, with either 2 mg/kg i.p. WAY100135, a 5-HT1A antagonist or 0.25 mg/kg i.p. ritanserin, a 5-HT2 antagonist. These results indicate that 5-HT in the ZI exerts its inhibitory effect on LH release via 5-HT1A receptors but that another 5-HT subtype may also be involved.

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Serotonergic Mediation of a Negative Feedback Effect of Estrogen on Luteinizing Hormone Release in Ovariectomized Rats*

Cited by 16 publications

References 30 publications

Differences in Ketanserin Binding in the Ventromedial Hypothalamus of Ewes Responsive or Refractory to Short Days

Differences in Ketanserin Binding in the Ventromedial Hypothalamus of Ewes Responsive or Refractory to Short Days

Changes in the 5-HT2Areceptor system in the pre-mammillary hypothalamus of the ewe are related to regulation of LH pulsatile secretion by an endogenous circannual rhythm

Serotonin Inhibits Luteinizing Hormone Release via 5-HT1A Receptors in the Zona incerta of Ovariectomised, Anaesthetised Rats Primed with Steroids

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