Reduced aminergic synthesis in the hypothalamus of the infertile, genetically diabetic (C57BL/KsJ-db/db) male mouse

Summary

Diabetes mellitus is commonly associated with reproductive neuroendocrinopathy in both humans and animal models for the disease. Diabetes-associated reproductive failure in the male is a result of multilevel dysfunction within the hypothalamo-pituitary-testicular axis. In view of the known effects of diabetes on hypothalamic gonadotropin-releasing hormone (GnRH) and gonadotropins in chemically-induced animal models for diabetes, we examined hypothalamic aminergic activities (important to the regulation of GnRH release), circulating gonadotropin levels and testicular morphology in the infertile, genetically diabetic (C57BL/KsJ-db/db) male mouse. Groups of 2–5 month old (average age: 3.4 months) and 6–11 month old (average age: 8.8 months) diabetic mice were compared with age-matched non-diabetic (C57BL/KsL-+/?) male mice. Diabetic mice in both age groups were markedly obese and hyperglycemic. Hypothalamic serotonin synthesis was inhibited in the preoptic area-anterior hypothalamus (POA-AH) in both 2–5 month old and 6–11 month old diabetic mice as well as in the mediobasal hypothalamus-median eminence (MBH-ME) of 6–11 month old diabetic mice. Catecholamine synthesis (norepinephrine and dopamine) was reduced in the POA-AH of 2–5 month old diabetic mice and in the MBH-ME of 6–11 month old mice. These aminergic changes were associated in 2–5 month old diabetic mice with reduced circulating levels of LH and in 6–11 month old diabetic mice, of both LH and FSH. In 6–11 month old diabetic mice, testes were characterized by a thickened tunica albuginea, numerous Sertoli cells and the near absence of any spermatogenic cells. The epididymis from these diabetic mice was devoid of spermatozoa. In considering the central role played by these hypothalamic amine systems in regulating GnRH release and thus reproductive function, these results suggest, at least in part, an explanation for the infertility associated with the genetically diabetic male mouse.