Plasma ACTH and corticosteroid levels were measured in normal subjects during constant infusion of either 0.9% (W/V) NaCl solution or cortisol, and during insulin-induced hypoglycaemia. During infusions of 0.9% NACl solution the secretion of ACTH and corticosteroids was episodic. Fast, rate-sensitive, negative feedback inhibition of ACTH secretin was observed during cortisol infusions, when the corticosteroid levels were within the physiological range (200-750 nmol/l) and were rising at a rate of between 5 and 10 nmol/l per min for 30 min or longer. When plasma corticosteroid levels were in a steady state, the initial fast feedback effects were abolished and ACTH secretion resumed. However, this recovery of ACTH secretion was not seen when the corticosteroid levels were persistently above 800 nmol/l. It appears that corticosteroid-induced negative feedback in man may be both rate- and level-sensitive. During insulin stress test ACTH secretion fell at time when the plasma corticosteroid level was rising rapidly (greater than 5 nmol/1 per min) despite persistent hypoglycaemia.
Luteinizing hormone from the pituitaries of women of premenopausal (Pre-M) and postmenopausal (Post-M) age has been studied to further understand the variations in the quality of plasma LH in women of different ages. The median and range for bioactive LH was 101: 85-155 IU/mg protein and 83: 52-201 IU/mg protein for the Pre- and Post-M groups respectively. The ratios of LH bioactivity/immunoreactivity (B:I) were 1.04 +/- 0.13 (Pre-M) and 0.97 +/- 0.02 (Post-M). Broad range isoelectrophoretic profiles of the pituitary extracts revealed a heterogeneous population of coincident bioactive and immunoreactive LH peaks. Recoveries from the columns were similar in both groups and B:I values of the LH material throughout the columns were between 0.5 and 2.0 in over 90% of the fractions. Between 31.8 and 36.6% of the LH from both groups appeared between pH 7 and pH 8. The most striking difference between the two groups was that greater than 34% of the bioactive LH from the Post-M pituitaries, but less than 6% of the LH from the other group had migrated as a major discrete peak to an acidic region of pH less than 6. We conclude that although there is no difference in total LH activity in the pituitaries from the two groups, substantially more 'acidic' LH material is stored in the postmenopausal pituitaries. These observations are consistent with the recent finding of greater circulating levels of acidic LH in plasma from post-menopausal women.
Thyrocytes isolated from porcine thyroids by mechanical and enzymatic dispersion and cultured in Eagle's minimal essential medium, supplemented with 5% (v/v) fetal calf serum, glutamine and cortisol, formed a continuous monolayer within 48 h. This monolayer was without cytochemical peroxidase and diaphorase (NADPH reoxidation) activity. In the presence of bovine thyrotrophin (bTSH; 50 mu./l) the cells developed a follicular-like architecture which was maximal at 4 days before reverting back to a uniform monolayer at 6 days. There were no detectable changes in the total DNA content over this period. The follicular structures had marked diaphorase and peroxidase activity, the latter being apically distributed. Concomitant with follicle formation bTSH induced uptake and organification of iodide presented to the cells during the last 6 h of culture. The extent of this process depended on the dose of bTSH and the duration of stimulation. The most sensitive effects for both iodide uptake and organification occurred with 1 mu. bTSH/l and were maximal with 100 mu./l. Uptake and organification were increased 20 +/- 8-fold and 9.6 +/- 2-fold (n = 10) respectively over the control with 100 mu./l and the doses of bTSH at which a half maximal response was seen (ED50) were 15 +/- 2 and 7 +/- 1 (S.D) mu./l (n = 10) respectively. On changing the culture medium to a serum-free system using HB101 culture medium the stimulation time for the most sensitive bTSH effect was reduced to 2.5 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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