Development of preovulatory follicles was studied during the oestrous cycle in two experiments designed to examine the effects of short-term lack of insulin on preovulatory follicular function and (Expt 2 only) ovulation. In Expt 1, on day 12 of the third postpubertal oestrous cycle, insulin treatment was discontinued in streptozocin-induced diabetic gilts (n = 4), and on day 18, ovaries were removed from the diabetic gilts and from four normal untreated gilts. Diabetic gilts had a higher percentage of macroscopically atretic follicles (29.4 versus 6.8%; SEM = 5.9, P < 0.03) than did normal gilts. Binding of 125I-labelled hCG by freshly collected granulosa cells from non-atretic follicles was similar in diabetic and normal gilts. Diabetic gilts had more LH peaks in 3 h on days 12-17 of the oestrous cycle than did normal gilts (2.3 versus 1.6; SEM = 0.12; P < 0.01). Serum oestradiol and progesterone concentrations were not affected by treatment, but serum testosterone was increased (P < 0.01) in diabetic gilts. In Expt 2, insulin treatment was withdrawn from nine diabetic gilts on day 12 of the oestrous cycle and ten normal gilts served as controls. On day 18, ovaries were removed from six diabetic and six normal gilts; four normal and three diabetic gilts were ovariectomized 25 days after oestrus. Follicular diameter of diabetic gilts tended to be smaller than that of control (control: 3.95 versus diabetic: 3.01 mm; SEM = 0.4, P < 0.08) and the proportion of follicles with histologic evidence of atresia was higher in diabetic gilts (control: 29 versus diabetic: 47%; SEM = 5; P < 0.05) on day 18. In both experiments, the insulin-like growth factor I (IGF-I) and oestradiol concentrations of follicular fluid of diabetic gilts untreated with insulin from day 12 to day 18 was lower than in nondiabetic gilts. After day 18 in Expt 2, normal gilts exhibited oestrus (duration of cycle was 20 +/- 0.5 days) accompanied by preovulatory surges in oestradiol and LH, whereas diabetic gilts did not exhibit oestrus or ovulate. In diabetic gilts, oestradiol concentrations were lower compared with those of normal gilts, and LH patterns were characterized by two (two gilts) or three (one gilt) increases of more than 2 ng ml-1 between day 18 and day 25. Thus, impaired follicular function in diabetic gilts is not explained by decreased function of the hypothalamo-pituitary axis, since LH was not decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes mellitus was induced using streptozotocin in five gilts between 8 and 12 weeks of age. Gilts were maintained with exogenous insulin (INS) except during experimental periods. Four litter-mate gilts served as controls. At 9 months of age, all gilts were ovariectomized, and 30 days after ovariectomy, Experiment (Exp) 1 was conducted. Jugular vein catheters were inserted and blood samples were collected every 10 min for 8 hr. Experiment 2 was conducted when gilts were 11 months of age. Venous blood and cerebrospinal fluid (CSF) samples were collected in the absence (Phase I) or presence (Phase II) of INS therapy. In Experiment 1, plasma glucose concentrations were greater (P < 0.05) in diabetic (465 +/- 17 mg/100 ml) than in control (82 mg +/- 17 mg/100 ml) gilts, whereas serum INS was lower (P < 0.0001) in diabetic gilts (0.3 +/- 0.02 vs 0.9 +/- 0.05 ng/ml) and insulin-like growth factor-I was similar in diabetic and control gilts (32 +/- 3 vs 43 +/- 4 ng/ml, respectively). Mean serum GH concentration was 2-fold greater (P < 0.02) in diabetics (2.8 +/- 0.4 ng/ml) than in control gilts (1.2 +/- 0.2 ng/ml). Diabetic gilts exhibited a greater (P < 0.05) number of GH pulses than control gilts (3.2 +/- 0.4 vs 1.5 +/- 0.3/8 hr, respectively). In addition, GH pulse magnitude was markedly elevated (P < 0.02) in diabetic (5.8 +/- 0.4 ng/ml) compared with control gilts (3.3 +/- 0.6 ng/ml). Mean basal serum GH concentrations were greater (P < 0.07) in diabetic (2.2 +/- 0.5 ng/ml) compared with control gilts (1.0 +/- .1 ng/ml). In Experiment 2, CSF concentrations of insulin-like growth factor-I, INS, GH, and protein were similar for diabetic and control gilts in both phases. Serum GH levels were similar for diabetics and controls in Phase I, but were greater (P < 0.05) in diabetics than in controls in Phase II. CSF glucose levels were greater in diabetic than in control gilts in both the presence (P < 0.003) and absence (P < 0.0002) of INS therapy, whereas plasma glucose was greater (P < 0.003) in diabetic than in control gilts in the absence of INS, but returned to control concentrations in the presence of INS. However, serum GH levels were unchanged after INS therapy in the diabetic gilts. In conclusion, altered GH secretion in the diabetic gilt may, in part, be due to elevated CSF glucose concentrations, which may alter GH-releasing hormone and/or somatostatin secretion from the hypothalamus.