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  • Author: J Fawcett x
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Results of experiments using steroid injections or implants have indicated that pituitary gonadotrophin secretion is not only modified by a change in perfusion rate of the releasing factors (RF) of luteinizing hormone (LH) and follicle-stimulating hormone, but that steroid feedback directly at the pituitary level may be involved in the cyclic regulation of gonadotrophin secretion (Ramirez, Abrams & McCann, 1964; Harris & Campbell, 1966; Arimura & Schally, 1971). Consequently, it has been suggested that pituitary responsiveness to LH-RF might change during the oestrous cycle as a result of variation in steroid secretion (Antunes-Rodrigues, Dhariwal & McCann, 1966). This experiment investigates this possibility.

Female Sprague—Dawley rats weighing 220–250 g and maintained under a lighting régime of 14 h light: 10 h darkness at a temperature of 21 ± 2 °C were used. Only animals showing at least two consecutive 4-day oestrous cycles were studied. LH-RF-evoked stimulation of LH release was examined

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RG Bennett, J Fawcett, MC Kruer, WC Duckworth and FG Hamel

A consequence of insulin-dependent diabetes mellitus is the loss of lean muscle mass as a result of accelerated proteolysis by the proteasome. Insulin inhibition of proteasomal activity requires interaction with insulin-degrading enzyme (IDE), but it is unclear if proteasome inhibition is dependent merely on insulin-NIDE binding or if degradation of insulin by IDE is required. To test the hypothesis that degradation by IDE is required for proteasome inhibition, a panel of insulin analogues with variable susceptibility to degradation by IDE binding was used to assess effects on the proteasome. The analogues used were [Lys(B28), Pro(B29)]-insulin (lispro), [Asp(B10)]-insulin (Asp(B10)) and [Glu(B4), Gln(B16), Phe(B17)]-insulin (EQF). Lispro was as effective as insulin at inhibition of degradation of iodine-125 ((125)I)-labeled insulin, but Asp(B10) and EQF were somewhat more effective. All agents inhibited cross-linking of (125)I-insulin to IDE, suggesting that all were capable of IDE binding. In contrast, although insulin and lispro were readily degraded by IDE, Asp(B10) was degraded more slowly, and EQF degradation was undetectable. Both insulin and lispro inhibited the proteasome, but Asp(B10) was less effective, and EQF had little effect. In summary, despite effective IDE binding, EQF was poorly degraded by IDE, and was ineffective at proteasome inhibition. These data suggest that insulin inhibition of proteasome activity is dependent on degradation by IDE. The mechanism of proteasome inhibition may be the generation of inhibitory fragments of insulin, or by displacement of IDE from the proteasome.

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The quantitative determination of exophthalmogenic activity in pituitary fractions by means of a cross-over bioassay in Carassius auratus is described.

The ratio of exophthalmogenic to thyrotrophic activity of eight bovine pituitary fractions has been determined.

Contrary to previous claims no dissociation of the two biological activities could be demonstrated.

Reasons for the discrepancy are discussed.