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[Estrogen resistance and aromatase deficiency in humans]
Cesare Carani1, Matteo Fabbi, Lucia Zirilli
1Département de Médecine Interne, Chaire d'Endocrinologie, Université de Modène, Italie.
Abstract:
The primordial role of estrogens in female reproductive function is well known. The recent production of transgenic mice deficient in estrogen receptors (ERKO) or in aromatase (ArKO) and the discovery in man of inactivating mutations of the corresponding genes (ER) have contributed to the understanding of the role of estrogens in metabolic processes in female as well as male. To date 8 well documented cases (5 women and 3 men) of congenital deficiencies in estrogens have been reported. As mice deficient in ERa had been previously described, these cases definitely proved that estrogen absence was compatible with survival and disproved the "lethality concept" previously held because the role of estrogens in implantation and gestation maintenance. ERKO mice are phenotypically normal though sterile, but their bone density is lower (20-25%) than that of controls. Similarly, men with no aromatase or no ER display continuous growth, osteoporosis and also (but not necessarily) alterations in testicular functions. How much do primordial functions such as bone development, control of gonadotrophin secretion and lipid metabolism depend on estrogens? These interrogations, elegantly clarified following testosterone and estradiol treatment in an aromatase deficient man are considered in this present synthesis.
Insights
Estrogen deficiency is compatible with survival, challenging previous concepts. This study explores estrogen
Area of Science:
- Endocrinology
- Reproductive Biology
- Metabolic Research
Background:
- Estrogens are crucial for female reproduction.
- Transgenic models (ERKO, ArKO) and human genetic mutations reveal broader roles.
- Congenital estrogen deficiencies in humans are rare but informative.
Purpose of the Study:
- To investigate the essential roles of estrogens in metabolic processes in both sexes.
- To clarify the dependence of primordial functions on estrogen signaling.
- To synthesize current knowledge on estrogen deficiency.
Main Methods:
- Review of documented cases of congenital estrogen deficiency (5 women, 3 men).
- Analysis of data from estrogen receptor knockout (ERKO) and aromatase knockout (ArKO) mice.
- Consideration of clinical observations and treatment responses in affected individuals.
Main Results:
- Estrogen absence is compatible with survival, refuting the 'lethality concept' regarding reproduction.
- ERKO mice show reduced bone density (20-25%) and sterility.
- Individuals with aromatase or estrogen receptor deficiency exhibit continuous growth, osteoporosis, and potential testicular dysfunction.
Conclusions:
- Estrogens are vital for bone development, gonadotropin secretion control, and lipid metabolism.
- Estrogen deficiency impacts multiple physiological systems beyond reproduction.
- Further research is needed to fully elucidate estrogen's multifaceted roles.