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

James, Margaret D.; Hole, David R.; Wilson, Catherine

doi:10.1159/000125169

Cited by 49 publications

(17 citation statements)

References 23 publications

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“…Hypothalamic areas were dissected according to the method of Palkovits (48) using the Paxinos and Watson stereotaxic atlas of the rat brain (49). The areas collected were the POA, VMN, ARC/ME and 21 and the coordinates were as reported previously (50). The micropunch samples were stored at -80 'C until RNA extraction or estimation of GAD activity.…”

Section: Methodsmentioning

confidence: 99%

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Leigh

Carter

Horton

et al. 1990

J Neuroendocrinology

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The possibility that steroids exert their effects on luteinizing hormone (LH) and prolactin release and female sexual behaviour via altering 7-arninobutyric acid (GABA) synthesis within the hypothalamus was investigated. Ovariectomized rats were treated with e$ther oil, 5 pg oestradiol benzoate (OB) or 5 pg OB plus 0.5 mg progesterone (P) 48 h later; autopsy was carried out 54 h after the OB injection. At this time, both steroid treatments stimulated prolactin release and lordotic activity. OB alone exerted a negative feedback effect on LH release while OB plus P stimulated an LH surge.The brains of the rats in these three treatment groups were microdissected and glutamic acid decarboxylase messenger ribonucleic acid (GAD mRNA) was estimated in specific hypothalamic areas obtained from individual brains; these areas included the preoptic area (POA), ventromedial nucleus (VMN), anterior medial portion of the zona incerta (ZI) and the arcuatehedian eminence area (ARC/ME). GAD mRNA concentrations were assessed by the slot-blotting technique and expressed as a ratio of GAD mRNA: b-actin mRNA.Both steroid treatments significantly reduced GAD mRNA in the ARCIME and ZI and OB plus P also reduced the concentration in the POA, while OB alone had no effect in this area. Neither treatment affected GAD mRNA in the VMN. These results indicate that when steroids stimulate LH and prolactin release and female sexual behaviour, they reduce GABA activity probably by reducing GABA synthesis in the POA, ZI and ARCIME. This suggests that GABA normally has an inhibitory influence on these parameters. G4BA synthesis does not however, appear to be involved in the negative feedback effects of steroids on LH release as measured 54 h after OB treatment.;,-,iminobutyric acid (GABA) is widely distributed in the hypothalmius with its highest concentrations in the preoptic area (POA) aiid ventromedial nucleus (VMN) (1 -3). GABA-containing neurons possess steroid receptors (4, 5 ) and it has becn suggested that sri:roids might exert some of their CNS effects via GABAergic s! stems (6-9). These effects include the control of luteinizing hormone (LH) and prolactin release and sexual behaviour. Rep x t s in the literature indicate that GABA can influence sexual bchaviour in females (10, 11) and has a dual effect on the release of I €1 and prolactin (12, 13). The results show that GABA is inhibitory to LH release in the POA and anterior medial portion o!' the zona incerta (ZI) (14-17). The site of it's stimulatory effect is not really known, although some data indicate that it may be in the medial basdl hypothalamus (12,18,19). Within the hypothalaIlIus GABA stimulates prolactin release, but it is inhibitory at the level of the pituitary (12)(13)(14)20). There are many reports investigating the inter-relationship of the gonadal steroids and GABA, in particular noting the effect of oestrogen and progesterone (P) on GABA activity in specific brain areas. Since GABA is present in both neuronal and glial tissue (1, 21) changes in its concentra...

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Section: Methodsmentioning

confidence: 99%

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Leigh

Carter

Horton

et al. 1990

J Neuroendocrinology

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“…For example, the majority of pharmacological studies indicate that 5-HT exerts chronic inhibition over lordotic responding [2][3][4]; however, other studies show that some 5-HT agonists can facilitate lordosis [5,6], In addition, gonadal hormone treatments, which are sufficient to induce lordosis, dif ferentially effect serotonergic activity in the areas which provide the descending circuitry for lordotic regulation. In the medial preoptic nucleus (mPOA), 5-HT activity is increased while in the ventromedial nucleus (VMN) and midbrain central gray area (MCG) 5-HT activity is de creased after progesterone administration to estrogenprimed females [7][8][9]. Thus, both pharmacological and neurochemical studies suggest that 5-HT exerts multiple and complex influences over lordotic responding.…”

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confidence: 99%

Serotonin, Catecholamines and Metabolites in Discrete Brain Areas in Relation to Lordotic Responding on Proestrus

Luine¹

1993

Neuroendocrinology

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Levels of serotonin (5-HT) and metabolite, 5-hydroxyindole-acetic acid (5-HIAA), dopamine and metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and norepinephrine (NE) were measured in microdissected brain areas at 14.30 and 19.30 h on diestrus and proestrus in rats. Lordosis, sexual behavior, was exhibited only by proestrous females at 19.30 h. The content of monoamines and/or metabolites changed from afternoon to early evening of diestrus in a number of brain regions. On proestrus, during the time when females became sexually receptive, additional changes appeared and many diestrous changes were reversed or amplified. Proestrus-specific changes were found in areas provinding the descending circuit for regulation of lordosis, the medial preoptic nucleus (mPOA), ventromedial nucleus of the hypothalamus (VMN) and midbrain central gray (MCG), and in areas outside of endocrine control centers such as parietal cortex (Ctx) and dorsal raphe nucleus (DR). Thus, these data are consistent with previous studies showing functional changes in monoaminergic transmitters during the day/night cycle and during hormonal induction of neuroendocrine events. NE levels increased between 14.30 and 19.30 h on proestrus in most brain areas, ranging from 20% increases in mPOA and Ctx to a 220% increase in the DR. NE levels decreased on proestrus in the VMN. The direction of proestrous changes in NE were reversed in some, but not all of the areas, between the afternoon and evening of diestrus. Dopamine was detectable in all areas sampled, and the metabolites HVA and DOPAC were detectable in some but not all areas. In the mPOA, DOPAC increased 100% during proestrus but was unchanged during the same period on diestrus suggesting a facilitatory effect of dopamine on lordosis in this area. Dopamine terminals in the MCG may inhibit behavior since HVA increased 150% between 14.30 and 19.30 h on diestrus and decreased 40% during the same interval on proestrus. For the serotonergic system, 5-HIAA levels increased 45% in the mPOA and 200% in the MCG from the afternoon to evening of proestrus but did not change on diestrus. In the VMN, 5-HIAA increased 60% between 14.30 and 19.30 h on diestrus but did not change during the same time on proestrus. 5-HIAA also increased 580% in the DR nucleus and 70% in the Ctx during proestrus but not diestrus. These data are consistent with previous studies suggesting that 5-HT terminals regulate lordosis responding on proestrus through hormone-dependent modulations at both facilitatory and inhibitory sites. In the VMN, where 5-HT inhibits lordosis, gonadal hormones appear to decrease the availability of 5-HT, and in the mPOA and MCG, where 5-HT may facilitate lordosis, gonadal hormones appear to increase the availability of 5-HT.

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“…In this report we show that the ZI may be another important site. Based on our previous findings in which 5-HT activity in the ZI was inversely correlated with LH release [9], we made the assumption that 5-HT would inhibit LH release when applied to this area, and, indeed, we found that administration of 5-HT bilaterally into the ZI at 2 µg inhibited the LH surge normally induced by oestrogen plus P. 8-OH-DPAT mimicked the effect indicating that 5-HT1A receptors were involved. These receptors are likely to be sited post-synaptically since BMY7378, another 5-HT1A agonist with a greater affinity for presynaptic receptors [46], did not affect LH release.…”

Section: Discussionmentioning

confidence: 99%

“…Investigations into the relationship of 5-HT activity and LH release can be divided into two types: one involves noting changes in endogenous 5-HT activity in the CNS at times of altered LH release and the other is by measuring changes in LH release after pharmacological manipulation of 5-HT activity. Focusing on the former method, we have shown previously that 5-HT activity in the ZI, as assessed by measuring 5-HT and 5-hydroxy-indole acetic acid (5- HIAA) in steroid-primed ovariectomised rats, is inversely related to LH release [9]. Thus, in rats treated with oestradiol benzoate (OB) alone, which suppressed LH release, the ratio of 5-HIAA:5-HT was increased compared to oil-treated controls, while after treatment with OB followed by progesterone which induced an LH surge, there was a concomitant reduction in both 5-HT and 5-HIAA concentrations in the ZI.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, in rats treated with oestradiol benzoate (OB) alone, which suppressed LH release, the ratio of 5-HIAA:5-HT was increased compared to oil-treated controls, while after treatment with OB followed by progesterone which induced an LH surge, there was a concomitant reduction in both 5-HT and 5-HIAA concentrations in the ZI. Using a submaximal steroid priming regime, we showed that the ratio of 5-HIAA:5-HT in the ZI was inversely correlated to the levels of LH in the plasma [9]. This work indicated that release of 5-HT in the ZI area has an inhibitory effect on LH release.…”

Section: Introductionmentioning

confidence: 99%

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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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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

Cited by 49 publications

References 23 publications

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Serotonin, Catecholamines and Metabolites in Discrete Brain Areas in Relation to Lordotic Responding on Proestrus

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

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