Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity

Kinyua, Ann W.; Doan, Khanh V.; Yang, Dong; Huynh, My Khanh Q.; Choi, Yun Hee; Shin, Dong Min; Kim, Ki Woo

doi:10.1038/s41598-018-23298-2

Cited by 30 publications

(20 citation statements)

References 41 publications

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“…Indeed, rapid infant weight gain has been associated with higher levels of the androgens androstrenedione and dehydroepiandrosterone sulfate at age 8 years in children without CF . These heightened levels might indicate premature adrenal activation through insulin stimulation, a process which could trigger earlier bone maturation and pubertal development. In a similar way, this mechanism of early exaggerated androgen production may be responsible for the earlier pubertal onset observed in obese children accompanied by reduced height gain in adolescence .…”

Section: Discussionmentioning

confidence: 99%

Rapid early increase in BMI is associated with impaired longitudinal growth in children with cystic fibrosis

Hak

Arets

Ent

et al. 2019

Pediatric Pulmonology

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Background We aimed to assess whether final height in children with cystic fibrosis (CF) is affected by body mass index (BMI), BMI increase, pulmonary function, and cystic fibrosis‐related diabetes (CFRD). Study design A longitudinal, retrospective study was performed in a cohort of 57 patients with CF (30 boys, 27 girls) born between 1997 and 2001. Height and weight were recorded annually from ages 0.5 to 10 years and biannually up to the age of 18. Measurements were converted to height‐for‐age‐adjusted‐for‐target‐height (HFA‐TH) and BMI‐for‐age z‐scores. Analyses were performed using the independent t tests and the Pearson's correlation. Results For both boys and girls, HFA‐TH and BMI‐for‐age z‐scores were significantly lower in the first year of life, these scores increased rapidly until the age of 11 and 8 years, respectively. In boys, HFA‐TH z‐scores declined during puberty, with subsequently significantly impaired final height (z‐score, −0.56, n = 30, standard deviation [SD] = 0.81, P = 0.001). In girls, HFA‐TH z‐scores briefly declined after the age of 8 years, but then increased to a z‐score of −0.21 (n = 27, SD = 0.87) at age 18, which is not significantly lower than the national average (P = 0.22). Pulmonary function and the presence of CFRD were not associated with final height. However, rapid BMI increase between ages 1 and 6 was negatively associated with final height in boys (n = 29, r =−0.420; P = 0.023) and girls (n = 25, r =−0.466; P = 0.019). Conclusions In boys and girls, early BMI increase was associated with impaired final height. We suggest that early childhood serves as a “window” in which nutritional variations may program subsequent growth. Further refinement of nutritional strategies could be needed.

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Section: Discussionmentioning

confidence: 99%

Rapid early increase in BMI is associated with impaired longitudinal growth in children with cystic fibrosis

Hak

Arets

Ent

et al. 2019

Pediatric Pulmonology

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“…Potential mechanisms of obesity-associated hyperandrogenemia include insulin resistance, enhanced androgen production in an expanded fat mass, and potential effects of abnormal adipokine/cytokine levels. Kinyua et al [151] suggested that insulin upregulates steroidogenic factor-1 (transcriptional factor) and the steroidogenic genes directly, independent of the CRH-ACTH-MC2R-PKA pathway. This increases the generation of adrenal gland hormones.…”

Section: Insulinmentioning

confidence: 99%

Associations of Obesity with Linear Growth and Puberty

Shalitin

Gat-Yablonski

2021

Horm Res Paediatr

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Background: The prevalence of obesity in childhood has increased dramatically in recent decades with increased risk of developing cardiometabolic and other comorbidities. Childhood adiposity may also influence processes of growth and puberty. Summary: Growth patterns of obesity during childhood have been shown to be associated with increased linear growth in early childhood, leading to accelerated epiphyseal growth plate (EGP) maturation. Several hormones secreted by the adipose tissue may affect linear growth in the context of obesity, both via the growth hormone IGF-1 axis and via a direct effect on the EGP. The observation that children with obesity tend to mature earlier than lean children has led to the assumption that the degree of body fatness may trigger the neuroendocrine events that lead to pubertal onset. The most probable link between obesity and puberty is leptin and its interaction with the kisspeptin system, which is an important regulator of puberty. However, peripheral action of adipose tissue could also be involved in changes in the onset of puberty. In addition, nutritional factors, epigenetics, and endocrine-disrupting chemicals are potential mediators linking pubertal onset to obesity. In this review, we focused on interactions of obesity with linear growth and pubertal processes, based on basic research and clinical data in humans. Key Message: Children with obesity are subject to accelerated linear growth with risk of impaired adult height and early puberty, with its psychological consequences. The data highlight another important objective in combatting childhood obesity, for the prevention of abnormal growth and pubertal patterns.

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“…Some of these states show features common to metabolic syndrome such as hypertension, insulin resistance, and visceral obesity [ 5 ]. Furthermore, HPA axis activity and the release of steroid hormones can be modulated by factors regulating feeding behavior [ [6] , [7] , [8] ].…”

Section: Introductionmentioning

confidence: 99%

Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state

Werdermann

Berger

Scriba

et al. 2021

Molecular Metabolism

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Objective Metabolic diseases are an increasing problem in society with the brain-metabolic axis as a master regulator of the human body for sustaining homeostasis under metabolic stress. However, metabolic inflammation and disease will trigger sustained activation of the hypothalamic-pituitary-adrenal axis. In this study, we investigated the role of metabolic stress on progenitor cells in the hypothalamic-pituitary-adrenal axis. Methods In vitro , we applied insulin and leptin to murine progenitor cells isolated from the pituitary and adrenal cortex and examined the role of these hormones on proliferation and differentiation. In vivo , we investigated two different mouse models of metabolic disease, obesity in leptin-deficient ob/ob mice and obesity achieved via feeding with a high-fat diet. Results Insulin was shown to lead to enhanced proliferation and differentiation of both pituitary and adrenocortical progenitors. No alterations in the progenitors were noted in our chronic metabolic stress models. However, hyperactivation of the hypothalamic-pituitary-adrenal axis was observed and the expression of the appetite-regulating genes Npy and Agrp changed in both the hypothalamus and adrenal. Conclusions It is well-known that chronic stress and stress hormones such as glucocorticoids can induce metabolic changes including obesity and diabetes. In this article, we show for the first time that this might be based on an early sensitization of stem cells of the hypothalamic-pituitary-adrenal axis. Thus, pituitary and adrenal progenitor cells exposed to high levels of insulin are metabolically primed to a hyper-functional state leading to enhanced hormone production. Likewise, obese animals exhibit a hyperactive hypothalamic-pituitary-adrenal axis leading to adrenal hyperplasia. This might explain how stress in early life can increase the risk for developing metabolic syndrome in adulthood.

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Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity

Cited by 30 publications

References 41 publications

Rapid early increase in BMI is associated with impaired longitudinal growth in children with cystic fibrosis

Rapid early increase in BMI is associated with impaired longitudinal growth in children with cystic fibrosis

Associations of Obesity with Linear Growth and Puberty

Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state

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