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A. L. C. WALLACE
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B. D. STACY
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G. D. THORBURN
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SUMMARY

The rate of removal of immunoreactive, intravenously injected 125I-labelled sheep growth hormone (GH) was used to calculate metabolic clearance rates (MCR) in two foetal lambs at 130 days of gestation and in two 6-day-old lambs. The mean MCR calculated for the foetuses was 2·9 ml/min/kg and for the lambs 3·1 ml/min/kg. The concentration of GH in plasma sampled before injection was determined immunologically and the values were used to calculate production rates. A production rate of 924 ng GH/min was calculated for the foetuses and 85 ng GH/min for the lambs. The effect of sectioning the pituitary stalk was studied in two foetuses; after the operation there was a rapid decrease in the circulating levels of GH. Hypophysectomy in two other foetuses also caused an abrupt decrease in plasma GH concentration.

It was concluded from these experiments that the exceptionally high concentrations of GH in the plasma of foetal lambs could not be attributed to impaired removal of the hormone from the circulation. The direct cause of the increased hormone concentrations was a high rate of GH secretion resulting from active stimulation of the foetal pituitary by the hypothalamus.

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A. L. C. WALLACE
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B. D. STACY
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G. D. THORBURN
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Since there are in-vivo effects of growth hormone (GH) on cartilage and adipose tissue which cannot be duplicated in vitro (Salmon & Daughaday, 1957; Daughaday & Reeder, 1966; Goodman, 1968) it has been postulated that pituitary GH is modified in the body before exerting its peripheral action.

In sheep, labelled GH is altered by the kidneys and returned to the circulation in an immunologically modified form (Wallace, Stacy & Thorburn, 1969). The altered material may still be biologically active and responsible for some of the observed effects of pituitary GH. We used the fat mobilizing action of GH in sheep (Bassett & Wallace, 1966) to test whether nephrectomy had an effect on the biological activity of injected GH.

The sheep were fasted for 24 h before the start of all experiments and throughout the experimental period. Blood samples were collected into heparinized tubes from jugular cannulae inserted the day before

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B. D. STACY
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A. L. C. WALLACE
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R. T. GEMMELL
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B. W. WILSON
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SUMMARY

Techniques of kidney micropuncture and electron microscope autoradiography have been used to study the uptake of 125I-labelled sheep growth hormone (GH) in rat renal proximal tubules. After microperfusion of a proximal tubule with 125I-labelled GH, the transport of label by the tubular epithelium was studied autoradiographically at selected times up to 1 h. The sequential transfer of labelled material from tubule to microvilli, then to small and large apical vacuoles and finally to lysosomes followed the pattern of absorption that has been described for other proteins. Evidence of lysosomal degradation of the transported protein was obtained from studies in vitro; lysosomes isolated from the renal cortex rapidly converted 125I-labelled GH to products of lower molecular weight. In addition to the absorptive pathway through the intracellular vacuolar apparatus it appeared that there was also an alternative pathway, less well defined, whereby GH could be absorbed without being degraded.

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