Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis

Prange‐Kiel, Janine; Jarry, Hubertus; Schoen, Michael; Kohlmann, Patrick; Lohse, C.; Zhou, Lepu; Rune, Gabriele M.

doi:10.1083/jcb.200707043

Cited by 111 publications

(86 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data obtained stimulating cells directly with LH further support this hypothesis. The final event of GnRH action is the enhancement of E2 synthesis that is registered after 24, 48, and 72 h. Our results are in agreement with data obtained by Prange-Kiel et al [19] on rat hippocampal slices and primary cells treated with GnRH. In fact also in these rat samples GnRH acts with a bell shaped dose response curve and the final steroid synthesized is estradiol.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells

Rosati

Sturli

Cungi

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

a b s t r a c tNeurosteroids are involved in Central Nervous System development, brain functionality and neuroprotection but little is known about regulators of their biosynthesis. Recently gonadotropins, Gonadotropin-releasing Hormone (GnRH) and their receptors have been localized in different brain regions, such as hippocampus and cortex.Using human neuronal-like cells we found that GnRH up-regulates the expression of key genes of cholesterol and steroid synthesis when used in a narrow range around 1.0 nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50% after 90 min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90 min and by 3.5 times after 3 h, respectively. GnRH action is mediated by LH and 1.0 nM GnRH enhances the expression of LH␤ as well.A two fold increase of cell cholesterol is induced after 90 min of GnRH incubation and 17␤-estradiol (E2) production is increased after 24, 48 and 72 h. These data indicate for the first time that GnRH regulates both cholesterol and steroid biosynthesis in human neuronal-like cells and suggest a new physiological role for GnRH in the brain.

show abstract

Section: Discussionsupporting

confidence: 93%

“…In M17 cells GnRH induces an up-regulation of the LH␤ subunit [17] and LH mediates neuronal pregnenolone production increasing Steroidogenic Acute Regulatory protein (StAR) expression [18]. Moreover, GnRH regulates estrogen synthesis and spine synapse density in rat primary hippocampal cultures [19].…”

Section: Introductionmentioning

confidence: 99%

Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells

Rosati

Sturli

Cungi

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

show abstract

“…27 GnRH was found to regulate the expression of pre-and post-synaptic markers spinophilin, synaptophisin and Egr1 in neurons obtained from hippocampus. 25,28 Hippocampal GnRHR has been implicated in the regulation of aromatase activity, 28 suggesting that the observed neurotrophic effect of GnRH could be mediated by a possible intervention on local synthesis of estrogen, known to affect synaptogenesis and expression of both spinophilin and synaptophysin. 29 This observation also suggests that estrus cycle -dependent synaptogenesis, occurring in the rat female hippocampus, may be regulated by the cyclic release of hypothalamic GnRH.…”

Section: Discussionmentioning

confidence: 99%

Physiology of Gonadotropin-Releasing Hormone (Gnrh): Beyond the Control of Reproductive Functions

Maggi¹

2016

MOJAP

View full text Add to dashboard Cite

Abbreviations: cAMP, cyclic adenosine monophosphate; DAG, diacylglycerol; IP3, inositol 1,4,5-triphosphate; HPG, hypothalamic-pituitary-gonadal; APP, amyloid precursor protein; MAPK, mitogen-activated protein kinase; ERK1/2, extracellular signal-regulated kinase; PI3K, phosphatidylinositol-3-kinase; EGR1, early growth response 1; PP, phosphotyrosine phosphatase; NF-Kb, nuclear factor kappa-light-chain-enhancer of activated b cells; DHCR24, 3-betahydroxysterol delta-24-reductase; St AR, steroidogenic acute regulatory protein; IKK-β, inhibitor of nuclear factor kappa-b kinase subunit beta; Aβ, amyloid beta peptide IntroductionGonadotropin releasing hormone (GnRH) is 35year-old neuropeptide recognized as the central regulator of reproductive functions.1 It was actually one of the earliest hypothalamic-releasing hormones sequenced and characterized and led its discoverer Andrew Schally to be awarded by the Nobel prize in 1977. 2 The peptide is a sequence of ten aminoacids ( Figure 1A) with a cyclized proline at the N-terminal and a glycine-amide residue at C-terminal, which confer some resistance to terminal peptidases.In mammals, GnRH is mainly produced by a limited number of hypothalamic neurons, which do not form a defined nucleus but show a dispersed organization in the mediobasal hypothalamus. Making axonal contacts with the hypothalamo-hypophyseal portal vessels, GnRH neurons release the decapeptide in the bloodstream directed to the adenohypophysis in a pulsatile manner. 3 At the pituitary level, the decapeptide interact with specific G protein-coupled receptors (GnRHR) present on gonadotrope cells inducing the release of the two gonadotropins (LH, luteinizing hormone and FSH, follicle stimulating hormones) which in turn coordinate male and female gonadal functions promoting the folliculogenesis and the ovulation in female, the spermatogenesis in male, and the production of sex steroid hormones (estrogen, progesterone and testosterone) ( Figure 1B). 4,5 GnRHR may be coupled either to Gaq/11 or Gas subunits which activate different intracellular responses including cAMP and DAG/IP3 pathways, as well as the mitogen-activated protein kinase (MAPK) cascades. 6 The separate activation of Gaq/11 or Gas subunits, by changes in the frequency of decapeptide pulsatile release, is the basis for the differential control of gonadotropin release. 7The actions of GnRH on reproductive functions cover the whole lifespan and characterize the maturation, the pubertal activation and the adult functions of the hormonal hypothalamo-pituitary-gonadal axis. Because of its importance on reproductive functions, a series of synthetic analogues, with agonist or antagonist activities have been developed soon after GnRH identification (Table 1). 8,9The pharmacological approach with GnRH analogues has been so far limited to the induction of puberty or, more in general, for recovery of fertility through a pulsatile administration; on the contrary, a continuous administration of GnRH agonists or antagonist is used to block the gonadotropin r...

show abstract

“…It is clear that serum levels of estradiol control release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which in turn stimulates the follicle-stimulating hormone/luteinizing hormone secretion that enhances the synthesis of estradiol in ovarian granulose cells. It has been reported that GnRH receptors are abundant in the hippocampus (Prange-Kiel et al, 2008) and GnRH can also directly stimulate estradiol synthesis in the hippocampus, similar to its effect on granulose cells (Brandt et al, 2013). The mechanism by which MDMA induces greater neurotoxicity in females is likely due to gonadal steroid effects on the serotonergic mechanism through which MDMA acts.…”

Section: Sex Differences In Ecstasy-induced Toxicitymentioning

confidence: 97%

Sex differences in MDMA-induced toxicity in Sprague-Dawley rats

Soleimani¹

2015

View full text Add to dashboard Cite

SummaryRecent evidence demonstrates that female subjects show exaggerated responses to 3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our study was to evaluate sex differences and the role of endogenous gonadal hormones on the effects of MDMA. Fifty-six intact and gonadectomized male and female Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline treatment. Learning and memory were assessed using the Morris water maze (MWM). The expression of Bax and Bcl-2 in the hippocampus was detected by Western blotting. Behavioral analysis showed that MDMA led to memory impairment in both male and female rats. The female rats showed more sensitivity to impairment than the males, as assessed using all the memory parameters in the MWM. Ovariectomy attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats showed more impairment than Sex differences in MDMA-induced toxicity in Sprague-Dawley rats MDMA-treated intact male rats. Bcl-2 and Bax were down-regulated and up-regulated in MDMA-treated male and female rats, respectively. MDMA treatment in the orchiectomized rats led to upregulation of Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up-regulation of Bax and caused more expression of Bcl-2 compared with what was observed in the MDMA-treated intact female rats. In summary, female rats showed exaggerated responses to the effects of MDMA and this may be explained by endogenous gonadal hormones.

show abstract

Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis

Cited by 111 publications

References 63 publications

Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells

Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells

Physiology of Gonadotropin-Releasing Hormone (Gnrh): Beyond the Control of Reproductive Functions

Sex differences in MDMA-induced toxicity in Sprague-Dawley rats

Contact Info

Product

Resources

About