Reduced aminergic synthesis in the hypothalamus of the infertile, genetically diabetic (C57BL/KsJ-db/db) male mouse.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
King
T S
TS
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Rohrbach
D H
DH
D000818:Animals; D001679:Biogenic Amines / Q000096:biosynthesis*; D001835:Body Weight / Q000502:physiology; D002395:Catecholamines / Q000096:biosynthesis; D003429:Cross Reactions; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005640:Follicle Stimulating Hormone / Q000097:blood; D006062:Gonadotropins / Q000032:analysis / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011863:Radioimmunoassay; D012701:Serotonin / Q000096:biosynthesis; D013737:Testis / Q000473:pathology / Q000502:physiology
D001679:Biogenic Amines; D002395:Catecholamines; D006062:Gonadotropins; D012701:Serotonin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone