A Confocal Microscopic Study of Gonadotropin-Releasing Hormone (GnRH) Neuron Inputs to Dopaminergic Neurons Containing Estrogen Receptor α in the Arcuate Nucleus of GnRH-Green Fluorescent Protein Transgenic Mice

Mitchell, Valérie; Loyens, Anne; Spergel, Daniel J.; Flactif, Martial; Poulain, Pierre; Tramu, G.; Beauvillain, Jean-Claudé

doi:10.1159/000069511

Cited by 16 publications

(9 citation statements)

References 40 publications

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“…A similar level of TH cells containing ERα neurones during dioestrous (60–70%) was measured, as observed previously (27). Levels of coexpression increased during late pregnancy (to approximately 80%).…”

Section: Discussionsupporting

confidence: 89%

Expression of Ovarian Steroid Hormone Receptors in Tuberoinfundibular Dopaminergic Neurones During Pregnancy and Lactation

Steyn

Anderson

Grattan

2007

J Neuroendocrinology

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During late-pregnancy, tuberoinfundibular dopaminergic (TIDA) neurones, a critical component of the negative-feedback loop regulating prolactin secretion, become unresponsive to the stimulatory effects of prolactin. The change in TIDA responsiveness to prolactin at this time results in a decrease in dopamine secretion and a prolactin surge. As the onset of parturition and the antepartum prolactin surge depend on the withdrawal of progesterone in the presence of oestrogen, it is likely that ovarian steroid hormones mediate this change in TIDA responsiveness. To determine whether ovarian steroids can directly modulate TIDA activity, and whether changes of receptor numbers might contribute to overall steroid-regulation of these neurones, we investigated the level of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) expression within TIDA neurones during pregnancy and lactation. Animals were sacrificed on dioestrous, days 12, 19 and 21 of pregnancy and day 5 of lactation, and the proportion of TIDA neurones expressing ERalpha or PR, as well as the total number of PR expressing cells within the arcuate nucleus, was determined. Approximately 75% and 55% of tyrosine hydroxylase neurones expressed ERalpha and PR, respectively. Levels of steroid receptor expression within TIDA neurones remained fairly constant, except for an increase in ERalpha on days 12 and 19 of pregnancy compared to dioestrous and lactation day 5. The presence of steroid receptors on TIDA neurones during pregnancy and lactation supports the concept of a direct effect of steroid hormones on these neurones at this time. Thus, steroid hormones may directly act on TIDA neurones to regulate maternal prolactin secretion. The relatively stable level of expression during late pregnancy suggests that a shift in steroid receptor expression during late pregnancy does not contribute to the change in TIDA responsiveness to prolactin at this time.

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Section: Discussionsupporting

confidence: 89%

Expression of Ovarian Steroid Hormone Receptors in Tuberoinfundibular Dopaminergic Neurones During Pregnancy and Lactation

Steyn

Anderson

Grattan

2007

J Neuroendocrinology

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“…Alternatively, blockade of central PRLR (and/or that of the PRL surge) by ⌬1-9-G129R-hPRL could augment the magnitude of the LH surge by diminishing PRL-stimulated dopaminergic activity in the hypothalamus (80). Indeed, more than a third of GnRH neurons have been demon-strated to be subject to tonic inhibition by dopamine (78) that could originate from ARC TIDA neurons (81,82) or GABAergic kisspeptin neurons in the AVPV (79,83). Furthermore, P 4 is known to allosterically potentiate the effects of GABA on GABA A R (84).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Prolactin Regulation of Luteinizing Hormone Secretion in the Female Rat

Grachev

Goffin

et al. 2015

Endocrinology

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Prolactin (PRL) levels increase in response to long-term antipsychotic treatment that disrupts reproductive function. Recent evidence suggests that activation of central PRL receptors (PRLR) inhibits LH secretion and in ovariectomized rats. However, the mechanisms involved, the mode of LH secretion affected and relevance to hyperprolactinemia remain unknown. We therefore investigated the contribution of central PRL/PRLR signaling to the control of estradiol-induced surges of LH and PRL and pulsatile LH secretion under basal and hyperprolactinemic conditions. First, by subjecting ovariectomized estradiol-primed rats intracerebroventricularly administered with PRL to frequent blood sampling, we demonstrated that acute activation of hypothalamic PRLR disrupts pulsatile LH secretion. Pretreatment (intracerebroventricularly) with the pure PRLR antagonist, Δ1-9-G129R-hPRL, or the γ-aminobutyric acid receptor type A antagonist, bicuculline, blocked this effect. Next, we revealed that sustained blockade of hypothalamic PRLR using Δ1-9-G129R-hPRL augmented the magnitude of LH surges induced by estradiol benzoate and progesterone treatment and suppressed the concomitant surges of PRL. Finally, we determined that acute antagonism of central PRLR is insufficient to normalize the duration of the LH pulse interval prolonged as a result of hyperprolactinemia induced by chronic exposure to the atypical antipsychotic sulpiride. These data serve as the first evidence to suggest that PRL signaling through hypothalamic PRLR inhibits pulsatile secretion of LH in a γ-aminobutyric acid receptor type A-dependent fashion and tonically restrains the magnitude of the LH surge. Furthermore, our results indicate that transient blockade of hypothalamic PRL/PRLR signaling is not an effective strategy for restoring LH pulsatility perturbed by chronic hyperprolactinemia.

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“…Mitchell et al ( 10 ) reported an estrous cycle dependent variation in the number of contacts between GnRH processes and TH-IR neurons in the Arc, suggesting a hormone-dependent plasticity for the communication ( 10 ). A profound suppression of tyrosine hydroxylase mRNA expression ( 28 , 29 ), and phosphorylation ( 30 , 31 ) of this enzyme with activity reduction have been shown during lactation.…”

Section: Discussionmentioning

confidence: 99%

“…However, this lactation-related infertility is diminished by the decreasing demand for breast-feeding of the pups, and the pulsatile secretion of GnRH neurons returns. Previous studies described GnRH varicosities in contact with dopamine-synthesizing, tyrosine-hydroxylase-immunoreactive (TH-IR) neurons in the Arc ( 9 , 10 ). Mitchell et al ( 10 ) also suggested an estrous-cycle dependent plasticity for these connecting profiles by reporting their presence only in pro-estrus and estrus, but not in diestrus ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

GnRH Neurons Provide Direct Input to Hypothalamic Tyrosine Hydroxylase Immunoreactive Neurons Which Is Maintained During Lactation

et al. 2018

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Gonadotropin releasing hormone (GnRH) neurons provide neuronal input to the preoptic area (POA) and the arcuate nucleus (Arc), two regions involved critically in the regulation of neuroendocrine functions and associated behaviors. These areas contain tyrosine hydroxylase immunoreactive (TH-IR) neurons, which play location-specific roles in the neuroendocrine control of both the luteinizing hormone and prolactin secretion, as well as, sexually motivated behaviors. Concerning changes in the activity of GnRH neurons and the secretion pattern of GnRH seen under the influence of rising serum estrogen levels and during lactation, we tested the hypothesis that the functional state of GnRH neurons is mediated via direct synaptic connections to TH-IR neurons in the POA and Arc. In addition, we examined putative changes of these inputs in lactating mice and in mothers separated from their pups. Confocal microscopic and pre-embedding immunohistochemical studies on ovariectomized mice treated with 17β-estradiol (OVX+E2) provided evidence for direct appositions and asymmetric synapses between GnRH-IR fiber varicosities and TH-IR neurons in the POA and the Arc. As TH co-localizes with kisspeptin (KP) in the POA, confocal microscopic analysis was continued on sections additionally labeled for KP. The TH-IR neurons showed a lower level of co-labeling for KP in lactating mice compared to OVX+E2 mice (16.1 ± 5% vs. 57.8 ± 4.3%). Removing the pups for 24 h did not alter significantly the KP production in TH-IR neurons (17.3 ± 4.6%). The mean number of GnRH-IR varicosities on preoptic and arcuate TH cells did not differ in the three animal models investigated. This study shows evidence that GnRH neurons provide direct synaptic inputs to POA and Arc dopaminergic neurons. The scale of anatomical connectivity with these target cells was unaltered during lactation indicating a maintained GnRH input, inspite of the altered hormonal condition.

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A Confocal Microscopic Study of Gonadotropin-Releasing Hormone (GnRH) Neuron Inputs to Dopaminergic Neurons Containing Estrogen Receptor α in the Arcuate Nucleus of GnRH-Green Fluorescent Protein Transgenic Mice

Cited by 16 publications

References 40 publications

Expression of Ovarian Steroid Hormone Receptors in Tuberoinfundibular Dopaminergic Neurones During Pregnancy and Lactation

Expression of Ovarian Steroid Hormone Receptors in Tuberoinfundibular Dopaminergic Neurones During Pregnancy and Lactation

Hypothalamic Prolactin Regulation of Luteinizing Hormone Secretion in the Female Rat

GnRH Neurons Provide Direct Input to Hypothalamic Tyrosine Hydroxylase Immunoreactive Neurons Which Is Maintained During Lactation

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