Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals
The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of which are affected in patients with Prader–Willi (PWS) and Schaaf–Yang syndrome (SYS). PWS is caused by paternal deletion, materna...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13109 |
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| author | Maria Camila Hoyos Sanchez Tara Bayat Rebecca R. Florke Gee Klementina Fon Tacer |
| author_facet | Maria Camila Hoyos Sanchez Tara Bayat Rebecca R. Florke Gee Klementina Fon Tacer |
| author_sort | Maria Camila Hoyos Sanchez |
| collection | DOAJ |
| description | The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of which are affected in patients with Prader–Willi (PWS) and Schaaf–Yang syndrome (SYS). PWS is caused by paternal deletion, maternal uniparental disomy, or imprinting defects that lead to loss of expression of a maternally imprinted region of chromosome 15 encompassing non-coding RNAs and five protein-coding genes; SYS patients have a mutation in one of them, <i>MAGEL2</i>. Throughout life, PWS and SYS patients suffer from musculoskeletal deficiencies, intellectual disabilities, and hormonal abnormalities, which lead to compulsive behaviors like hyperphagia and temper outbursts. Management of PWS and SYS is mostly symptomatic and cures for these debilitating disorders do not exist, highlighting a clear, unmet medical need. Research over several decades into the molecular and cellular roles of PWS genes has uncovered that several impinge on the neuroendocrine system. In this review, we will discuss the expression and molecular functions of PWS genes, connecting them with hormonal imbalances in patients and animal models. Besides the observed hormonal imbalances, we will describe the recent findings about how the loss of individual genes, particularly <i>MAGEL2</i>, affects the molecular mechanisms of hormone secretion. These results suggest that <i>MAGEL2</i> evolved as a mammalian-specific regulator of hypothalamic neuroendocrine function. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:22:26Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3ea172af7b2146c6b0bd7c38d5753ae92023-11-19T08:12:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171310910.3390/ijms241713109Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in MammalsMaria Camila Hoyos Sanchez0Tara Bayat1Rebecca R. Florke Gee2Klementina Fon Tacer3School of Veterinary Medicine, Texas Tech University, 7671 Evans Dr., Amarillo, TX 79106, USASchool of Veterinary Medicine, Texas Tech University, 7671 Evans Dr., Amarillo, TX 79106, USASchool of Veterinary Medicine, Texas Tech University, 7671 Evans Dr., Amarillo, TX 79106, USASchool of Veterinary Medicine, Texas Tech University, 7671 Evans Dr., Amarillo, TX 79106, USAThe hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of which are affected in patients with Prader–Willi (PWS) and Schaaf–Yang syndrome (SYS). PWS is caused by paternal deletion, maternal uniparental disomy, or imprinting defects that lead to loss of expression of a maternally imprinted region of chromosome 15 encompassing non-coding RNAs and five protein-coding genes; SYS patients have a mutation in one of them, <i>MAGEL2</i>. Throughout life, PWS and SYS patients suffer from musculoskeletal deficiencies, intellectual disabilities, and hormonal abnormalities, which lead to compulsive behaviors like hyperphagia and temper outbursts. Management of PWS and SYS is mostly symptomatic and cures for these debilitating disorders do not exist, highlighting a clear, unmet medical need. Research over several decades into the molecular and cellular roles of PWS genes has uncovered that several impinge on the neuroendocrine system. In this review, we will discuss the expression and molecular functions of PWS genes, connecting them with hormonal imbalances in patients and animal models. Besides the observed hormonal imbalances, we will describe the recent findings about how the loss of individual genes, particularly <i>MAGEL2</i>, affects the molecular mechanisms of hormone secretion. These results suggest that <i>MAGEL2</i> evolved as a mammalian-specific regulator of hypothalamic neuroendocrine function.https://www.mdpi.com/1422-0067/24/17/13109PWSSYSimprintinghormone secretionsecretory granulehypothalamus |
| spellingShingle | Maria Camila Hoyos Sanchez Tara Bayat Rebecca R. Florke Gee Klementina Fon Tacer Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals International Journal of Molecular Sciences PWS SYS imprinting hormone secretion secretory granule hypothalamus |
| title | Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals |
| title_full | Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals |
| title_fullStr | Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals |
| title_full_unstemmed | Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals |
| title_short | Hormonal Imbalances in Prader–Willi and Schaaf–Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals |
| title_sort | hormonal imbalances in prader willi and schaaf yang syndromes imply the evolution of specific regulation of hypothalamic neuroendocrine function in mammals |
| topic | PWS SYS imprinting hormone secretion secretory granule hypothalamus |
| url | https://www.mdpi.com/1422-0067/24/17/13109 |
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