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11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the reversible metabolism of corticosterone to inert 11-dehydrocorticosterone. At least two isoforms exist. 11 beta-HSD-1, the first to be characterised and the only isoform for which a cDNA has been isolated, is highly expressed in liver, kidney and hippocampus. The activity of 11 beta-HSD in rat liver is higher in males, due to oestrogen repression of 11 beta-HSD-1 gene transcription in females. Sexual dimorphism in rodent liver proteins is frequently mediated indirectly via sex-specific patterns of GH release (continuous in females, pulsatile in males). We have now investigated whether this applies to 11 beta-HSD, using dwarf rats (congenitally deficient in GH) and hypophysectomised animals. 11 beta-HSD activity and 11 beta-HSD-1 mRNA expression in liver was significantly lower in control female than male rats (50% and 72% of male levels respectively). These sex differences in the liver were attenuated in dwarf rats, with both males and females showing similar levels of 11 beta-HSD activity to control males. Administration of continuous (female pattern) GH to dwarf male rats decreased hepatic 11 beta-HSD activity (30% fall) and mRNA expression (77% fall), whereas the same total daily dose of GH given in the male (pulsatile) pattern had no effect on hepatic 11 beta-HSD in female dwarf rats. Continuous GH also attenuated hepatic 11 beta-HSD activity (25% fall) and 11 beta-HSD-1 mRNA expression (82% fall) in hypophysectomised animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The release of oxytocin and neurophysin during suckling has been studied in conscious unrestrained guinea-pigs. After prior separation, mothers and litters were allowed to suckle for a period of 10 min, and the weight gain of the litter recorded as an index of milk transfer. Maternal blood samples were obtained without disturbance through previously implanted intravenous cannulae and neurophysin and oxytocin determined on unextracted plasma by specific and sensitive radioimmunoassays. In 82 out of 118 experiments the young gained weight during suckling (1.6 +/- 0.1 (S.E.M.) g/pup) and this was associated with large rises in both oxytocin and neurophysin concentrations in plasma (mean concentrations: oxytocin 65.4 fmol/ml, neurophysin 360 fmol/ml). Where serial samples were taken, oxytocin and neurophysin showed a rapid rise and fall in concentration closely associated with the occurrence of milk ejection as judged by the behaviour of the litter. The present results provide the first direct evidence of a spurt release of both oxytocin and neurophysin measured simultaneously during milk ejection. The conscious lactating guinea-pig thus provides a useful laboratory model in which to study hormone release during milk ejection.

The in-vivo biological activity of recombinant methionyl insulin-like growth factor I (met-IGF-I) was demonstrated in hypophysectomized rats by following blood glucose after an i.v. bolus injection of met-IGF-I; a dose-dependent decrease in blood sugar was seen. Membrane transport was studied using the non-metabolizable amino acid alpha-aminoisobutyric acid; stimulation was obtained with the highest dose used (90 micrograms/rat). To test the original somatomedin hypothesis, growth studies were performed in hypophysectomized rats. Two or three doses of met-IGF-I were given with three different administration regimes (i.v. or s.c. infusion, or s.c. injections twice daily) for 6 or 8 days. Little growth-promoting activity was observed, with a significant effect on body weight gain obtained only when met-IGF-I was given continuously at the highest dose used (180 micrograms/day). No effect was seen on the in-vivo uptake of radioactive sulphate into cartilage. Epiphyseal cartilage width increased slightly at the highest dose of met-IGF-I, but only when the hormone was given by infusion. When 180 micrograms met-IGF-I/day were given by injections, a significant effect on longitudinal bone growth was obtained (90 micron above control). The levels of IGF in the serum were not measurably increased after s.c. administration of met-IGF-I, whereas after i.v. infusion, significantly raised levels were obtained at the higher dose rates (3.0 +/- 0.3 and 2.8 +/- 0.1 units/ml). Growth hormone was much more effective than met-IGF-I even at 50-fold lower doses. Priming the animals with 10 mu. bovine GH/day followed by combined infusions of GH and met-IGF-I did not reveal any potentiating effects of met-IGF-I in the presence of GH. We conclude that met-IGF-I is a relatively poor growth-promoting agent when given systemically, and that somatomedins are more likely to act as local growth factors rather than as circulating mediators of the growth-promoting effects of GH.