BES2020 BES 2020 Novel model of sex steroid deficiency in mice to study the physiological effects of delayed and suppressed puberty (1 abstracts)
Novel model of sex steroid deficiency in mice to study the physiological effects of delayed and suppressed puberty
Na Ri Kim 1 , Khalil Rougin 1 , David Karel 1 , Antonio Leen 1 , Schollaert Dieter 1 , Deboel Ludo 1 , Van HerckErik 1 , Wardenier Nele 2 , Cools Martine 2 , Decallonne Brigitte 1 , Claessens Frank 3, , Dubois Vanessa 1, & Vanderschueren Dirk 1,
1Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism, and Ageing (CHROMETA), KU Leuven, Leuven, Belgium; 2Department of Internal Medicine and Pediatrics, Ghent University and Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, Ghent, Belgium; 3Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
*Contributed equally as last authors
Background: Sex steroids are critical for skeletal development and maturation during puberty as well as skeletal maintenance during adult life. However, the exact time during puberty when sex steroids have the highest impact as well as the ability of bone to recover from transient sex steroid deficiency is unclear. The latter is highly relevant in the clinical context of delayed puberty, since the impact of a delayed pubertal onset on adult bone health remains elusive. Surgical castration is a common technique to study sex steroid effects in rodents, but it is irreversible, invasive, and associated with metabolic and behavioral alterations. Hence, alternative approaches are needed to study timing and reversibility of sex steroid actions.
Methodology: We used a low dose (LD) or a high dose (HD) of gonadotropin-releasing hormone antagonist to either temporarily or persistently suppress sex steroid action in male mice, respectively. Growth, body composition and bone parameters were determined.
Results: The LD group, a model for delayed puberty, did not show changes in linear growth or body composition, but displayed reduced trabecular bone volume during puberty, which fully caught up at adult age. In contrast, the HD group, representing complete pubertal suppression, showed a phenotype reminiscent of that observed in surgically castrated rodents. Indeed, HD animals exhibited severely impaired cortical and trabecular bone acquisition, decreased body weight and lean mass, and increased fat mass. In addition, the HD group was characterized by an increased linear growth, which is reminiscent of the clinical observation in patients with hypogonadotropic hypogonadism.
Conclusions: We validated a new rodent model of chemical castration, which can be used as an alternative to surgical castration. Moreover, the transient nature of the intervention enables to study the effects of delayed puberty and reversibility of sex steroid deficiency. Our work suggests that, at least in mice, a delayed pubertal timing is associated with bone loss during puberty but this deleterious effect does not persist at adult age.
Volume 71
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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