The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their produc...The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.展开更多
Background Cushing＇s disease is a pituitary-dependent type of Cushing＇s syndrome. Treatment consists of pituitary surgery or radiotherapy, but the recurrence rate at 10 years is as high as 40%. Adrenalectomy is cons...Background Cushing＇s disease is a pituitary-dependent type of Cushing＇s syndrome. Treatment consists of pituitary surgery or radiotherapy, but the recurrence rate at 10 years is as high as 40%. Adrenalectomy is considered an effective treatment to refractory Cushing＇s disease. The objective of this study was to examine the efficacy of laparoscopic adrenalectomy and open adrenalectomy in Cushing＇s disease, focusing on reversing the sequelae of hypercortisolism and improving patients＇ quality of life. Methods Forty-three patients （29 women, 14 men） with recurrent Cushing＇s disease after transsphenoidal operation underwent laparoscopic （n=32） or open （n=11） adrenalectomy from 2000 to 2008. Surgical results were evaluated for all the 43 patients. Patients completed a follow-up survey, including the short-form 36-item （SF-36） health survey. Results All the 43 patients achieved clinical reversal of hypercortisolism after adrenalectomy. Time to symptom resolution varied from a few weeks to up to 3 years. Most physical changes had resolved by a mean of 8 months after surgery. These conditions were not significantly different between the laparoscopy and open groups. Median length of hospital stay was shorter in the laparoscopy group （4 vs. 9 days; P 〈0.001）. Median follow-up was 48.5 months. Of the 34 （79%） patients available for follow-up, 22 （65%） had adrenocorticotropic hormone levels 〉200 ng/ml and 6 （27%） had clinical Nelson syndrome. Four patients died by 75 months after surgery. Using SF-36, 30 （88%） patients reported they felt their health status was good to excellent compared with 1 year before adrenalectomy; however, they showed significantly lower scores in all the 8 SF-36 parameters compared with the general population. No significant difference emerged in SF-36 scores between the laparoscopy and open groups. Conclusions Adrenalectomy showed high survival and clinical benefits in recurrent Cushing＇s disease patients. Despite patient-reported improvement in health after adrenalectomy, patients continue to experience poor health status compared with the general population.展开更多
基金supported by the Key Research and Development Program of Guangxi(2021AB13014)Major Project of Guangxi Innovation Driven(AA18118016)+7 种基金National Key Research and Development Program of China(2017YFC0908000)Natural Key Research and Development Project(2020YFA0113200)National Natural Science Foundation of China(81770759,82060145,31970814)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2021JJA140912)Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University,Guangxi Key Laboratory for Genomic and Personalized Medicine(19-050-22,19-185-33,20-065-33,22-35-17)Major Project of Scientific Research and Technology Development Plan of Nanning(20221023)Guangxi Natural Science Foundation(2022GXNSFAA035641)Self-funded Project of Health Commission of Guangxi Zhuang Autonomous Region(Z-A20230620)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.
文摘Background Cushing＇s disease is a pituitary-dependent type of Cushing＇s syndrome. Treatment consists of pituitary surgery or radiotherapy, but the recurrence rate at 10 years is as high as 40%. Adrenalectomy is considered an effective treatment to refractory Cushing＇s disease. The objective of this study was to examine the efficacy of laparoscopic adrenalectomy and open adrenalectomy in Cushing＇s disease, focusing on reversing the sequelae of hypercortisolism and improving patients＇ quality of life. Methods Forty-three patients （29 women, 14 men） with recurrent Cushing＇s disease after transsphenoidal operation underwent laparoscopic （n=32） or open （n=11） adrenalectomy from 2000 to 2008. Surgical results were evaluated for all the 43 patients. Patients completed a follow-up survey, including the short-form 36-item （SF-36） health survey. Results All the 43 patients achieved clinical reversal of hypercortisolism after adrenalectomy. Time to symptom resolution varied from a few weeks to up to 3 years. Most physical changes had resolved by a mean of 8 months after surgery. These conditions were not significantly different between the laparoscopy and open groups. Median length of hospital stay was shorter in the laparoscopy group （4 vs. 9 days; P 〈0.001）. Median follow-up was 48.5 months. Of the 34 （79%） patients available for follow-up, 22 （65%） had adrenocorticotropic hormone levels 〉200 ng/ml and 6 （27%） had clinical Nelson syndrome. Four patients died by 75 months after surgery. Using SF-36, 30 （88%） patients reported they felt their health status was good to excellent compared with 1 year before adrenalectomy; however, they showed significantly lower scores in all the 8 SF-36 parameters compared with the general population. No significant difference emerged in SF-36 scores between the laparoscopy and open groups. Conclusions Adrenalectomy showed high survival and clinical benefits in recurrent Cushing＇s disease patients. Despite patient-reported improvement in health after adrenalectomy, patients continue to experience poor health status compared with the general population.
