Normal and Premature Adrenarche

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 42(6), P. 783 - 814

Published: March 31, 2021

Adrenarche is the maturational increase in adrenal androgen production that normally begins early childhood. It results from changes secretory response to adrenocorticotropin (ACTH) are best indexed by dehydroepiandrosterone sulfate (DHEAS) rise. These related development of zona reticularis (ZR) and its unique gene/enzyme expression pattern low 3ß-hydroxysteroid dehydrogenase type 2 with high cytochrome b5A, sulfotransferase 2A1, 17ß-hydroxysteroid 5. Recently 11-ketotestosterone was identified as an important bioactive adrenarchal androgen. Birth weight, body growth, obesity, prolactin ZR development. Adrenarchal androgens contribute onset sexual pubic hair (pubarche) sebaceous apocrine gland Premature adrenarche causes ≥90% premature pubarche (PP). Its cause unknown. Affected children have a significantly increased growth rate proportionate bone age advancement typically does not compromise potential. Serum DHEAS testosterone levels normal for female puberty. associated mildly risks insulin resistance, possibly mood disorder polycystic ovary syndrome. Between 5% 10% PP due virilizing disorders, which usually characterized more rapid adult height potential than adrenarche. Most cases nonclassic congenital hyperplasia. Algorithms presented differential diagnosis PP. This review highlights recent advances molecular genetic developmental biologic understanding insights into emanating mass spectrometric steroid assays.

Language: Английский

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Plasticity of the Maternal Vasculature During Pregnancy

Annual Review of Physiology, Journal Year: 2019, Volume and Issue: 81(1), P. 89 - 111

Published: Feb. 10, 2019

Maternal cardiovascular changes during pregnancy include an expansion of plasma volume, increased cardiac output, decreased peripheral resistance, and uteroplacental blood flow. These adaptations facilitate the progressive increase in perfusion that is required for normal fetal growth development, prevent development hypertension, provide a reserve anticipation significant loss associated with parturition. Each woman's genotype phenotype determine her ability to adapt response molecular signals emanate from fetoplacental unit. Here, we overview major hemodynamic then consider regional splanchnic, renal, cerebral, uterine circulations terms endothelial vascular smooth muscle cell plasticity. Although consideration gestational disease beyond scope this review, aberrant signaling and/or maternal responsiveness contribute etiology several common diseases such as preeclampsia, intrauterine restriction, diabetes.

Language: Английский

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Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders

Frontiers in Endocrinology, Journal Year: 2019, Volume and Issue: 10

Published: April 9, 2019

Memory dysfunction is a symptomatic feature of many neurologic and neuropsychiatric disorders; however, the basic underlying mechanisms memory altered states circuitry function associated with disorders remain vast unexplored territory. The initial discovery endogenous neurosteroids triggered quest to elucidate their role as neuromodulators in normal diseased brain function. In this review, based on perspective our own research, advances leading positive negative neurosteroid allosteric modulators GABA type-A (GABAA), NMDA, non-NMDA type glutamate receptors are brought together historical conceptual framework. We extend analysis toward state-of-the art view how modulation neural may affect deficits. By aggregating results from multiple laboratories using both animal models for disease human clinical research age-related neurodegenerative disorders, elements level begins emerge. Lastly, effects endogenously active exogenously administered networks across life span women men point possible pharmacological connectome by which these might act modulate diverse mind.

Language: Английский

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Adipose tissue estrogen production and metabolism in premenopausal women

The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2021, Volume and Issue: 209, P. 105849 - 105849

Published: Feb. 19, 2021

Although the ovaries produce majority of estrogens in women before menopause, estrogen is also synthesized peripheral tissues such as adipose tissue (AT). The typical female AT distribution, concentrated subcutaneous and femoro-gluteal regions, estrogen-mediated, but significance synthesis premenopausal poorly understood.Serum visceral homogenates from 28 undergoing non-malignant surgery were analyzed for estrone, estradiol, serum estrone sulfate (E1S) concentrations with liquid chromatography-tandem mass spectrometry. Isotopic precursors used to measure enzyme activities estrone-producing steroid sulfatase estradiol-producing 17β-hydroxysteroid dehydrogenases (17β-HSD). Messenger RNA (mRNA) expression levels genes estrogen-metabolizing enzymes using real-time reverse transcription quantitative polymerase chain reaction.While estradiol was predominant circulating active estrogen, dominated AT, a higher concentration than (median, 2657 vs 1459 pmol/kg; P = 0.002). Both depots converted E1S estradiol. Median five ten times (P < 0.001) level 1.3 0.005). local correlated positively mRNA aromatase (r 0.65, 0.003). Waist circumference increased production 0.60, 0.039).Premenopausal demonstrated high estrogenic activity considerable concentrations. This may be factor promoting female-typical distribution women.

Language: Английский

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ATP7A-Regulated Enzyme Metalation and Trafficking in the Menkes Disease Puzzle

Biomedicines, Journal Year: 2021, Volume and Issue: 9(4), P. 391 - 391

Published: April 6, 2021

Copper is vital for numerous cellular functions affecting all tissues and organ systems in the body. The copper pump, ATP7A critical whole-body, cellular, subcellular homeostasis, dysfunction due to genetic defects results Menkes disease. leads deficiency nervous tissue, liver, blood but accumulation other tissues. Site-specific deficiencies of lead loss function copper-dependent enzymes tissues, range disease pathologies observed can now be explained full by lack specific enzymes. New pathways involving activated lysosomal steroid sulfatases link patient symptoms usually related inborn errors metabolism Additionally, new roles lysyl oxidase activation molecules necessary innate immune system, novel adapter that play ERGIC trafficking brain receptors proteins, are emerging. We here summarize current knowledge enzyme disease, with a focus on ATP7A-mediated metalation secretory pathway. By establishing mechanistic relationships between processes patients will not only increase understanding biology also allow identification an expanding pathways. This raise awareness rare symptoms, thus aid early diagnosis patients.

Language: Английский

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