Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.

Abstract. A continuous infusion technique of either [3H]oestradiol-17β (E2) or unlabelled E2 was used to investigate suggested differences in the metabolic clearance rate of oestradiol-17β (MCR-E2) in immature and peripubertal female pigs. Using the isotope infusion technique, the following values were obtained: 60 day old gilts; MCR-E2 = 2133 ± 274 ([unk] ± sem) ml/min, MCR-E2/kg BW = 116 ± 14.5 ml/min kg, and conversion ratio (CR) of E2 to oestrone (E1) = 31.6 ± 3.7%. The respective values for 160 day old gilts were: MCR-E2 = 3027 ± 340, MCR-E2/kg BW = 48.5 ± 4.82, and CR = 15.9 ± 2.12. Except for a significant difference in the weight related MCR-E2 data for the 60 day old group, similar values were found following infusion of unlabelled E2. The percentage of radioactivity extractable with ether from plasma was 22.6 ± 3.0% and 27.2 ± 2.0%. Fifty-seven and 66% of total radioactivity infused was recovered in the urine within 12 h in 60 and 160 day old gilts, respectively. There was no difference in the percentage binding of E2 to plasma proteins as determined by equilibrium dialysis (80%). It is concluded that in addition to an activation of ovarian steroidogenesis during puberty, a gradual maturational decrease in the MCR-E2/kg BW might play a role in raising plasma E2 concentrations and thus in constituting an effective oestrogen feedback signal, which results in the first pre-ovulatory LH-surge.

An involvement of ovarian secretions and in particular oestradiol-17 beta in the maturation of the positive feedback mechanism controlling gonadotrophin surge secretion was studied in prepubertal gilts. The LH/FSH responses to an intramuscular injection of age- and body weight-related doses of oestradiol benzoate (OB) were compared in intact gilts at 60 days of age with or without oestradiol-17 beta pretreatment from 30 to 52 days of age. Four further groups of gilts were challenged with OB at 160 days and were intact, ovariectomized at 60 days, ovariectomized at 60 days and given oestrogen therapy from days 60 to 130 or ovariectomized at 130 days. A significant increase in the magnitude of LH surge responses to OB and a decrease in the time to the first consistent period of surge secretion in intact gilts at 160 compared to 60 days of age confirmed earlier studies and is considered to represent a real maturational change in positive feedback activity. A longer response interval was also present in the majority of ovariectomized gilts. Furthermore a significant reduction in the magnitude of OB-induced LH responses at day 160 occurred in gilts ovariectomized at day 60 compared to those ovariectomized at day 130 and with intact control animals. Oestrogen therapy after ovariectomy at day 60 effectively restored the magnitude of the LH response however. It is concluded that maturation of the positive feedback mechanism is ovarian, and probably oestrogen, dependent.