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1.
J Clin Endocrinol Metab ; 95(9): 4276-82, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20566621

ABSTRACT

OBJECTIVE: The role of testosterone in the regulation of metabolic and physiological function in men is well defined, but its role in women remains enigmatic. Thus, the present study sought to assess the contribution of endogenous circulating androgens to the regulation of metabolic function, body morphometry, and physical function in normal naturally postmenopausal women. METHODS: Using a cross-sectional design, we measured serum androgens in a cohort of 29 naturally postmenopausal women and correlated the results with metabolic, morphometric, and functional outcome parameters. These included insulin sensitivity, whole-body fat and lean body mass, visceral/abdominal fat areasm and aerobic capacity. RESULTS: Higher serum testosterone levels were related to greater maximal aerobic capacity and reduced adiposity. Additionally, higher serum dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, and androstenetriol glucuronidate levels were correlated to greater insulin sensitivity. CONCLUSION: In naturally postmenopausal women, endogenous androgens may play a role in the maintenance of beneficial patterns of metabolic, morphometric, and functional parameters.


Subject(s)
Androgens/blood , Body Weights and Measures , Metabolome , Postmenopause/blood , Postmenopause/physiology , Aged , Body Weights and Measures/statistics & numerical data , Cohort Studies , Cross-Sectional Studies , Female , Health , Health Status Indicators , Humans , Ideal Body Weight/physiology , Male , Middle Aged , Statistics as Topic , Testosterone/blood , Testosterone/physiology
2.
Am J Obstet Gynecol ; 194(1): 113-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16389019

ABSTRACT

OBJECTIVE: Uterine vascular remodeling at mid gestation includes the thinning of the vessel walls and, typically, an increase in lumen diameter. This study aimed to elucidate any differences in structural remodeling in normal murine pregnancies versus those differences that resulted from the crossing of CBA/J female mice by DBA/2 male mice, a combination that is known to exhibit recurrent resorption/pregnancy loss. STUDY DESIGN: CBA/J female mice that were pregnant by DBA/2 male mice (abnormals) and DBA/2 female mice that were pregnant by CBA/J male mice (normals) were killed at mid gestation, which is a time when fetal resorption can be identified. Tissues were collected for permanent fixation and gene expression studies with complementary DNA macroarrays that were specific for extracellular matrix proteins. A 2-fold increase in expression or a 50% decline was considered significant. Expression changes were confirmed by real-time reverse transcriptase-polymerase chain reaction. RESULTS: The vessel-to-lumen diameter ratios were found to be significantly greater for the CBA/J implantation sites (1.50 +/- 0.05 vs 1.22 +/- 0.02, respectively; P < .0001), which indicates a lack of vascular remodeling. There was also a trend towards smaller lumen diameters for the CBA/J vessels, but this was not statistically significant (78.2 +/- 4.4 microm vs 93.5 +/- 6.8 microm, respectively; P = .22). The mean coefficient of variation for lumen measurements was 0.8% and for vessel diameter was 0.3%. The ranges were 0 to 3.2% and 0 to 1.4%, respectively. Tissue inhibitor of metalloproteinase 2 expression was up-regulated in the placentas of the group with higher resorption rates when compared with normals. This was confirmed with reverse transcriptase-polymerase chain reaction, where abnormals exhibited 2.6-fold greater tissue inhibitor of metalloproteinase 2 protein quantities when compared with normal controls (P = .03). CONCLUSION: The expansive vascular remodeling of decidual vessels that is characteristic of normal murine pregnancy is attenuated significantly in the CBA/J x DBA/2 mating combination, which is known for its tendency to recurrent fetal resorption. This has been correlated with a relative overexpression of tissue inhibitor of metalloproteinase 2 protein in placentas of this strain combination and compared with normals.


Subject(s)
Arterioles/physiopathology , Chimera , Decidua/blood supply , Fetal Resorption/physiopathology , Mice, Inbred CBA , Mice, Inbred DBA , Tissue Inhibitor of Metalloproteinase-2/metabolism , Animals , Female , Fetal Resorption/metabolism , Fetal Resorption/pathology , Gene Expression Profiling , Male , Mice , Oligonucleotide Array Sequence Analysis , Placenta/metabolism , Placenta/pathology , Pregnancy , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tissue Inhibitor of Metalloproteinase-2/genetics
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