The response of plasma growth hormone to synthetic growth hormone-releasing factor (hpGRF-44) administered intravenously was examined in normal men of various ages ranging from 20 to 75 years. Most of the subjects who were over forty years old had either no or much lower response of plasma growth hormone to hpGRF-44. In contrast plasma growth hormone increased markedly after hpGRF-44 injection in all men in their twenties and thirties. The mean peak level of plasma GH following hpGRF-44 administration was 29.6 +/- 20.4 (SD) ng/ml in men in their twenties, 30.2 +/- 26.5 ng/ml in their thirties, 9.7 +/- 5.2 ng/ml in their forties, 10.9 +/- 5.4 ng/ml in their fifties, 8.4 +/- 4.8 ng/ml in their sixties and 8.1 +/- 7.5 ng/ml in their seventies. These results suggest that somatotroph cells become less sensitive to growth hormone-releasing factor with aging.

Background. Telomeric deletions contribute to genetic instability and may represent an important mechanism of carcinogenesis. Amplification of the c‐erbB‐2 gene has been demonstrated in breast carcinoma. The clinical significance of telomeric deletions and c‐erbB‐2 gene amplification therefore was studied in patients with breast disorders. Methods. The Southern blot analysis was used to measure telomeric length as well as the c‐erbB‐2 gene amplification of breast carcinomas, adjacent normal breast tissues, fibroadenomas, and cases of gynecomastia. Results. Significant reductions in telomeric length and concentration were observed in all breast tissues when compared to placental DNA. Mean telomeric lengths were lowest in carcinomas and fibroadenomas. There were no significant differences, however, in the telomeric lengths among tissues from patients with breast carcinomas, fibroadenomas, or gynecomastia. The degree of telomeric deletion correlated significantly with histologic grade and was most notable in Grade 3 (scirrhous) breast carcinoma. The extent of telomeric deletion reflects the histologic aggressiveness of breast carcinoma, and telomeric reduction already can be seen in the adjacent normal breast tissues from patients with breast cancer. c‐erbB‐2 gene amplification was observed in 26.8% of the patients with breast carcinoma. c‐erbB‐2 gene amplification was not observed, however, in patients with fibroadenomas or gynecomastia. The degree of telomeric deletion did not correlate with c‐erbB‐2 gene amplification, tumor size, clinical stage, steroid receptors, or prognosis. Telomeric length was shorter in lymph node‐negative tumors than in lymph node‐positive tumors. Conclusions. These findings indicate that a shorter telomere length reflects growth advantage in breast cancer tissue, and telomeric reduction may promote cancer progression. Cancer 1994; 73:2978–84.

The effect of FFA on GH-releasing hormone (GHRH)-mediated secretion of GH was examined in six normal young men. Three of the men were infused with 250 ml of a lipid-heparin solution at 1.67 ml/min for 150 min, and the other three were given an equivalent volume of saline in the same manner. Thirty minutes after the start of infusion, 100 micrograms GHRH (the 44-amino acid form) were injected iv, and plasma GH and FFA were measured. One week later, the same men participated in an identical experiment, but the ones who had received lipid-heparin previously were given saline and vice versa. In both experiments, plasma FFA increased to 2.25 +/- 0.16 meq/liter (mean +/- SEM) 60 min after the start of lipid-heparin infusion, whereas FFA levels did not change significantly in the saline-treated group. Mean plasma GH levels reached peak concentrations in both groups 30 min after GHRH treatment. However, the peak GH response when lipid-heparin was given was significantly diminished (8.4 +/- 1.7 ng/ml), compared with the peak response when saline was given (28.9 +/- 7.1 ng/ml). These data suggest that plasma FFA elevations induced by lipid-heparin infusion inhibit GH secretion induced by GHRH.

Maternal adrenocortical function was studied by measuring plasma cortisol and urinary free cortisol during gestation.