The biological characteristics of a growth hormone-releasing hormone (GHRH)-like substance produced by a pheochromocytoma were studied. Analysis by gel filtration chromatography combined with the use of two distinct GHRH antisera that recognize the N- and C-termini of authentic GHRH(1–44)NH2 indicated molecular heterogeneity of the immunoreactive GHRH in the tumor extract, but a component corresponding to GHRH(1–44)NH2 was the predominant form. The biological activity of this immunoreactive component was assessed in vitro by measuring its ability to induce growth hormone release from dispersed rat anterior pituitary cells. At concentrations of 0.125–2.0 nmol/l, the test materials induced a dose-related increase in growth hormone release from the cells into the incubation medium (range 992±68–1872±32 ng·1.7×105 cells−1·3 h−1), similar to that observed with synthetic GHRH(1–44)NH2 (control value 640±30 ng·1.7× 105 cells−1·3 h−1). This suggests that immunoreactive GHRH in the tumor has almost the same biological activity as the synthetic product and that a combination of pheochromocytoma and acromegaly is not always fortuitous because both diseases may be caused by a single neoplasm.

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The effects of an LHRH agonist (LHRHa), [D-Ser (tBu)]6 des-Gly-NH210 ethylamide, on endocrine function and the LHRH and LH/hCG receptors in the pituitary-gonadal axis were examined.The LHRHa was injected at 100ng/ 100g body weight into male rats once a day for 4 weeks and its effects were observed until 2 weeks after the end of treatment.Due to LHRHa treatment, the plasma LH concentration began to increase on day 3, reached a peak on day 7, and then decreased, although it remained above the control level during the treatment. The pituitary LH content decreased on day 1, reached a minimum (about 40% of the control) between days 3 and 7, and then was maintained at 60% of the control level until week 4. In contrast, the pituitary LHRH receptor concentration increased only on day 3, and the association constant (Ka) remained unchanged during the observation period. The testis weight and plasma testosterone concentration began to decrease on day 3, reached the minimum on day 7 and remained at this level until week 4, and their levels were not completely restored to normal 2 weeks after cessation of treatment.The testicular LH/hCG receptor concentration was decreased on day 1, and markedly decreased to 10-15% of the control value between day 7 and week 4, but the Ka value was slightly increased during the treatment.However, these values had completely recovered 2 weeks after the cessation of treatment. The testicular LHRH receptor concentration increased between days 1 and 7, returned to the control level in weeks 2 and 4, and then decreased 2 weeks after cessation of treatment.Its Ka value was reduced in weeks 2 and 4.These data suggest that the inhibitory effect of LHRHa on the gonad in male rats is not due to reduced pituitary LH release, but to changes in the number and Ka values of gonadal receptors for LH/hCG and LHRH.

The responses of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) to oral administration of L-dopa were studied in normal subjects and patients with various endocrine and metabolic diseases to clarify the pathophysiological role of the GHRH-GH axis. In normal subjects, the plasma GHRH concentration was increased from the basal value of 9.8 +/- 1.4 pg/ml (mean +/- SE) to 34.8 +/- 3.1 pg/ml at 30 approximately 90 min after oral administration of 500 mg L-dopa, followed by a rise of GH release (plasma GH level from less than 1 ng/ml to 21.7 +/- 4.7 ng/ml) in most cases, indicating that L-dopa stimulates GH secretion via hypothalamic GHRH. On L-dopa administration, no apparent increases in both plasma GHRH and GH concentrations were observed in patients with hypothalamic hypopituitarism, whereas GHRH administration induced almost normal GH response. In patients with acromegaly, the plasma levels of GHRH remained stationary after the L-dopa administration and did not correlate with plasma GH levels. In subjects with simple obesity, the responses of plasma GHRH (peak 13.2 +/- 1.2 pg/ml) and GH (peak 4.3 +/- 1.7 ng/ml) to L-dopa were significantly lower than those in normal subjects (p less than 0.01). In patients with primary hypothyroidism, peak levels of plasma GHRH (12.6 +/- 1.3 pg/ml) and GH (2.4 +/- 0.6 ng/ml) were significantly lower than those in normal subjects (p less than 0.01). In patients with non-insulin dependent diabetes mellitus (NIDDM), the responses of GHRH and GH were divided into 2 groups; in the responder the peak values of GHRH and GH were 19.4 +/- 8.6 pg/ml and 12.2 +/- 1.4 ng/ml and in the low or non responder 14.7 +/- 1.5 pg/ml and 2.0 +/- 0.6 ng/ml, respectively. Between both groups, there was a significant difference in the values of fasting blood sugar and HbA1 and mean suffering period. These findings suggest that GH secretion evoked by the L-dopa administration is induced by GHRH released from the hypothalamus, and impairment of GH secretion associated with simple obesity, primary hypothyroidism, or NIDDM may be in part attributed to insufficiency of GHRH release from the hypothalamus, and indicate that L-dopa test is clinically useful for evaluating the ability of intrinsic GHRH release in such diseased states.

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