The hypothalamic-pituitary-gonad axis in male Cushing’s disease before and after curative surgery

Zheng, Hangping; Wang, Qi; Cui, Qiaoli; Sun, Quanya; Wu, Wei; Ji, Lijin; He, Min; Lü, Bin; Zhang, Zhaoyun; Ma, Zengyi; Shen, Ming; Shou, Xuefei; Wang, Yongfei; Zhao, Yao; Li, Yiming; Ye, Hongying; Zhang, Shuo

doi:10.1007/s12020-022-03083-y

Cited by 11 publications

(2 citation statements)

References 9 publications

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“…Both low and high levels of circulating glucocorticoids (as reported in Cushing Syndrome or Addison disease) suppress male steroidogenesis and fertility, whilst normal physiological levels regulate testis function [ 46 , 47 ]. This study developed two distinct Cre/ LoxP models to target GR signalling in Leydig cells and showed that there is a threshold of GR inactivation to induce a Leydig cell defect (approximately 30% versus 50% GR targeting).…”

Section: Discussionmentioning

confidence: 99%

A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function

Gannon

Darbey

Chensee

et al. 2022

IJMS

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Glucocorticoids are steroids involved in key physiological processes such as development, metabolism, inflammatory and stress responses and are mostly used exogenously as medications to treat various inflammation-based conditions. They act via the glucocorticoid receptor (GR) expressed in most cells. Exogenous glucocorticoids can negatively impact the function of the Leydig cells in the testis, leading to decreased androgen production. However, endogenous glucocorticoids are produced by the adrenal and within the testis, but whether their action on GR in Leydig cells regulates steroidogenesis is unknown. This study aimed to define the role of endogenous GR signalling in adult Leydig cells. We developed and compared two models; an inducible Cre transgene driven by expression of the Cyp17a1 steroidogenic gene (Cyp17-iCre) that depletes GR during development and a viral vector-driven Cre (AAV9-Cre) to deplete GR in adulthood. The delivery of AAV9-Cre ablated GR in adult mouse Leydig cells depleted Leydig cell GR more efficiently than the Cyp17-iCre model. Importantly, adult depletion of GR in Leydig cells caused reduced expression of luteinising hormone receptor (Lhcgr) and of steroidogenic enzymes required for normal androgen production. These findings reveal that Leydig cell GR signalling plays a physiological role in the testis and highlight that a normal balance of glucocorticoid activity in the testis is important for steroidogenesis.

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Section: Discussionmentioning

confidence: 99%

A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function

Gannon

Darbey

Chensee

et al. 2022

IJMS

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“…Growth hormone deficiency and hypogonadotropic hypogonadism, two common pituitary hormone dysfunctions in both active CS and aging, maybe other important contributors to the elevated prevalence of muscle weakness in aged patients with cortisol excess [28,29]. Also, 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), which converts inactive cortisone into active cortisol, was up-regulated in healthy older women and associated with reduced grip strength, insulin resistance, and adverse body composition profile [30].…”

Section: Introductionmentioning

confidence: 99%

Cushing's Syndrome in the Elderly

Zdrojowy-Wełna,

Valassi

2024

Exp Clin Endocrinol Diabetes

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Management of Cushing’s syndrome (CS) can be particularly challenging in older patients, due to the lack of several clinical features associated with cortisol excess along with a greater burden of comorbidities in them, as compared with the younger. Moreover, interpretation of diagnostic tests could be influenced by age-related physiological changes of cortisol secretion. While mortality is higher and quality of life is more impaired in the elderly with CS as compared with the younger, there is currently no agreement on the most effective therapeutic options in aged individuals, and safety data concerning medical treatment are scanty. In this review, we summarize the current knowledge about age-related differences in etiology, clinical presentation, treatment and outcomes of CS, and describe the potential underlying mechanisms.

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Cushing’s disease and bone

Zdrojowy-Wełna,

Stachowska,

Bolanowski

2024

Pituitary

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Bone impairment associated with Cushing’s disease (CD) is a complex disorder, mainly involving deterioration of bone quality and resulting in an increased fracture rate, often despite normal bone mineral density. Bone complications are common in patients with CD at the time of diagnosis but may persist even after successful treatment. There is currently no agreement on the optimal diagnostic methods, thresholds for anti-osteoporotic therapy and its timing in CD. In this review, we summarize the current data on the pathophysiology, diagnostic approach and management of bone complications in CD.

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The hypothalamic-pituitary-gonad axis in male Cushing’s disease before and after curative surgery

Cited by 11 publications

References 9 publications

A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function

A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function

Cushing's Syndrome in the Elderly

Cushing’s disease and bone

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