Peak Incremental Responses Research Articles

Hormone Ontogeny in the Ovine Fetus and Neonate. XXII. The Effect of Somatostatin on the Growth Hormone (GH) Response to GH-Releasing Factor*

We postulated that an increase in the biological effectiveness of somatostatin (SRIF) accounts, at least in part, for the decrease in basal and GRF-induced ovine GH (oGH) secretion observed around birth in the ovine fetus and neonate. To test this hypothesis, SRIF (SRIF-14; given as 30 micrograms/kg iv bolus, followed by 2 micrograms/kg.min for 75 min) was infused into chronically catheterized fetal and neonatal lambs, and the oGH response induced by GRF [GRF-(1-44) amide; 1 microgram/kg] in the presence of exogenous SRIF was compared to the oGH response induced by GRF in saline-infused controls. In fetuses of 115-122 days gestation, SRIF had no detectable effect on the oGH response to GRF [peak incremental oGH response (mean +/- SEM), 527 +/- 124 vs. 562 +/- 103 ng/ml in controls]. In neonatal lambs (3-17 days old), SRIF completely suppressed the immediate oGH response to GRF (peak incremental response, 0.8 +/- 1.3 vs. 111 +/- 34 ng/ml in controls; P less than 0.02). In late gestational fetuses (126-139 days old), a transitional pattern was observed (peak incremental oGH response, 207 +/- 56 vs. 324 +/- 30 ng/ml in controls; P less than 0.04). In the second part of this study, we explored, in the neonatal lamb, the hypothesis that SRIF withdrawal plays a role in pulsatile GH secretion and that the amount of GRF to which the somatotrope is exposed before SRIF withdrawal is a major factor in determining the amplitude of GH bursts. SRIF (SRIF-14; a 30 micrograms/kg bolus, followed by 2 micrograms/kg.min) was infused iv for 40 min, GRF [GRF-(1-44) amide; 1 microgram/kg] was injected iv 20 min after starting the SRIF infusion, and the oGH rise after SRIF withdrawal was evaluated. In one series of controls GRF was replaced by saline, and in the other SRIF was replaced by saline. The oGH rise during recovery after SRIF alone was lower than that after the combined administration of SRIF and GRF (peak oGH increment, 8 +/- 3 vs. 38 +/- 12 ng/ml; P less than 0.04). The amplitude of the GH pulse after SRIF and GRF was similar to the immediate oGH response to GRF alone. These studies show that SRIF is unable to suppress the immediate oGH response to GRF in the ovine fetus, and that the suppressive effect of SRIF on the immediate oGH response to GRF increases gradually in late gestation and sharply at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects on the pituitary-thyroid axis and prolactin secretion of single and repetitive oral doses of thyrotropin-releasing hormone (TRH).

ABSTRACT The effects of single and repetitive oral doses of synthetic TRH were studied in healthy young men and women. Administration of single doses of TRH, from 2.5 to 160 mg, to each of 18 subjects resulted in increasing maximum increments in serum levels of thyrotropin (TSH), thyroxine (T4, triiodothyronine (T3), and prolactin. The peak incremental responses were these: maximum Δ TSH, 27.1 ± 2.6 μU/ml (to the 80 mg TRH dose); maximum Δ T3, 113 ± 19 ng/100 ml (160 mg); maximum Δ T4, 4.2 ± 0.3 μg/100 ml (160 mg); maximum Δ prolactin in women 46.2 ± 8.2 ng/ml (80 mg); and the maximum Δ prolactin in men, 35.0 ± 3.9 ng/ml (80 mg). Administration of 10 mg of TRH every 8 hr for 22 consecutive doses to each of 9 normal young women resulted in raised mean serum T3 and T4 concentrations, which reached new steady-state levels in 4 and 3 days. The new steady-state T3 levels were approximately 30% higher than the pretreatment T3 level, and the new steady-state T4 levels were approximately 40% higher than the pretr...