ABSTRACT
Mature cystic teratomas (dermoid cysts) of the ovary are very rarely associated with androgen production. The source of androgens in these cysts may be tumours such as Sertoli-Leydig cell tumour or Leydig cell hyperplasia. In this study, we present a case of virilisation in a postmenopausal female patient, where Leydig cell hyperplasia in a mature cystic teratoma was found to be responsible for the production of testosterone. In addition, extensive areas of lipomatous differentiation were identified. These areas showed significant alterations in adipocytic morphology, and differential diagnoses such as spindle cell lipoma (SCL) and atypical lipomatous tumour (ALT) were excluded after additional workup. Adipose tissue is traditionally described as an energy reservoir, but recently it has become clear that adipose tissue is a complex endocrine organ with additional metabolic roles in whole body homeostasis. Exuberant proliferation of lipomatous tissue in this teratoma raises the possibility of a synergistic role of Leydig cells and adipocytes in the development of hyperandrogenism.
ABSTRACT
Here, we investigated how LDL receptor deficiency (Ldlr(-/-)) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham-operated Ldlr(-/-) mice fed Western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and TG profiles, castrated mice were resistant to diet-induced obesity and had improved glucose metabolism and reduced plasma TG levels, despite a further deterioration in their plasma cholesterol profile. The effect of hypogonadism on diet-induced weight gain of Ldlr(-/-) mice was independent of ApoE and Lrp1. Indirect calorimetry analysis indicated that hypogonadism in Ldlr(-/-) mice was associated with increased metabolic rate. Indeed, mitochondrial cytochrome c and uncoupling protein 1 expression were elevated, primarily in white adipose tissue, confirming increased mitochondrial metabolic activity due to thermogenesis. Testosterone replacement in castrated Ldlr(-/-) mice for a period of 8 weeks promoted diet-induced obesity, indicating a direct role of testosterone in the observed phenotype. Treatment of sham-operated Ldlr(-/-) mice with the aromatase inhibitor exemestane for 8 weeks showed that the obesity of castrated Ldlr(-/-) mice is independent of estrogens. Overall, our data reveal a novel role of Ldlr as functional modulator of metabolic alterations associated with hypogonadism.
