title: Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men.
abstract: Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect.
authors.affiliation: Reproductive Endocrine Unit, BHX 511, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
authors.forename: Nelly
authors.initials: N
authors.lastname: Pitteloud
authors.forename: Megan
authors.initials: M
authors.lastname: Hardin
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Dwyer
authors.forename: Elena
authors.initials: E
authors.lastname: Valassi
authors.forename: Maria
authors.initials: M
authors.lastname: Yialamas
authors.forename: Dariush
authors.initials: D
authors.lastname: Elahi
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Hayes
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D007985:Leydig Cells / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000378:metabolism*; D049629:Waist-Hip Ratio
chemical_list: D020738:Leptin; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D007986:Luteinizing Hormone