Pregnancy and lactation differentially modify the transcriptional regulation of steroidogenic enzymes through DNA methylation mechanisms in the hippocampus of aged rats

Rossetti, María Florencia; Varayoud, Jorgelina; Lazzarino, Gisela Paola; Luque, Enrique H.; Ramos, Jorge G.

doi:10.1016/j.mce.2016.03.037

Cited by 22 publications

(25 citation statements)

References 98 publications

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“…Such methylation constitutes an important mechanism of transcriptional regulation. Accordingly, changes in the methylation patterns of specific sites located in 5αR‐1 gene CpG island were correlated with alterations in the mRNA levels in the rat hippocampus .…”

Section: Steroidogenic Enzymes In the Brainmentioning

confidence: 96%

“…Recently, Rossetti et al . proposed that the transcriptional regulation of the 3α‐HSD gene in the rat brain would be mediated by differential methylation mechanisms . Particularly, they found that the promoter was mostly methylated at a potential binding site for the sterol regulatory element‐binding protein (SREBP–) and this change was correlated with alteration in the mRNA levels , suggesting that SREBP– also affects gene expression.…”

Section: Steroidogenic Enzymes In the Brainmentioning

confidence: 99%

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Oestrogens and Progestagens: Synthesis and Action in the Brain

Rossetti

Cambiasso

Holschbach

et al. 2016

J Neuroendocrinology

107

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When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side-chain cleavage, 3b-hydroxysteroid dehydrogenase/D5-D4 isomerase, cytochrome P450arom, steroid 5a-reductase and 3a-hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.

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Section: Steroidogenic Enzymes In the Brainmentioning

confidence: 96%

Section: Steroidogenic Enzymes In the Brainmentioning

confidence: 99%

Oestrogens and Progestagens: Synthesis and Action in the Brain

Rossetti

Cambiasso

Holschbach

et al. 2016

J Neuroendocrinology

107

View full text Add to dashboard Cite

show abstract

“…During pregnancy, a larger amount of progesterone is produced to control the physiological status of the body so as to maintain pregnancy. P450scc has been shown to play a pivotal role in the synthesis of progesterone, and loss of function of P450scc can lead to reduced levels of progesterone [16,17]. Estrogen also has an essential role in the maintenance and development of pregnancy [16].…”

Section: Discussionmentioning

confidence: 99%

“…P450scc has been shown to play a pivotal role in the synthesis of progesterone, and loss of function of P450scc can lead to reduced levels of progesterone [16,17]. Estrogen also has an essential role in the maintenance and development of pregnancy [16]. CYP19, which functions upstream of LRH-1, regulates the expression of LRH-1 and has pivotal roles in the synthesis of estrogen.…”

Section: Discussionmentioning

confidence: 99%

“…Experiments in a mouse model using LRH-1 knockout found that LRH-1 can regulate ovulation [15]. Progesterone synthesis during pregnancy is important for the maintenance of pregnancy, and cholesterol side-chain cleavage enzyme (P450scc) catalyzes the synthesis of progesterone [16,17]. CYP19, which is also called aromatase cytochrome P450, is the key rate-limiting enzyme involved in the synthesis of estrogen.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Liver Receptor Homolog-1 (LRH-1) in Villi and Decidua of Patients with Unexplained Recurrent Spontaneous Abortion

Hou

et al. 2017

Med Sci Monit

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BackgroundIn view of the important function of nuclear receptor liver receptor homolog 1 (LRH 1) in various biological processes and the physiological changes accompanying unexplained recurrent spontaneous abortion (USRA), our study was carried out to investigate the potential roles of LRH-1 in USRA.Material/MethodsThirty patients with URSA at early the early state of pregnancy were selected, and 30 patients with normal early pregnancy were also selected from Aug 2015 to Sep 2016 as a control group. The expression of LRH-1 protein in decidua and villi were detected by immunohistochemistry and Western blot analysis, and the expression of LRH-1 mRNA was detected by RT-PCR. The expression levels of CYP19 and P450scc were detected by RT-PCR and Western blot analysis at mRNA and protein levels, respectively.ResultsThe levels of LRH-1, CYP19, and P450scc mRNA and protein in villi of the patients in the URSA group were significantly lower than in the control group. There were no significant differences between the URSA group and control group in the levels of LRH-1, CYP19, and P450scc mRNA and protein in villi in decidua.ConclusionsURSA was related to the reduced expression level of LRH-1 in villous tissues but not in decidua, and expression of LRH-1 may be related to the expression of CYP19 and P450scc. We believe that the expression level of LRH-1 can be used as a marker in the early diagnosis of URSA, and the regulation of LRH-1 expression many lead to new URSA treatments.

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