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Five groups (n = 11) of 250-g female rats were oophorectomized and immediately thereafter received daily sc injections of estradiol benzoate (EB; 0.05, 0.5, 5.0, and 50.0 micrograms) or vehicle for 28 days. A sixth group underwent sham operation and received injections of vehicle. Somatomedin-C (SmC) concentrations were determined before EB administration. After 4 weeks of EB treatment, the GH response to human GH-releasing factor (1-44) (GRF; 5 micrograms/kg, iv) was determined under pentobarbital anesthesia in seven animals from each group. Serum PRL, LH, and estradiol and plasma SmC concentrations were also measured. The GH secretory response to GRF (delta GH) was greatest in castrated animals receiving vehicle (P less than 0.05) and was significantly blunted in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.05) compared to that in sham-operated animals. A significant negative correlation was observed between delta GH and serum PRL concentrations (r = -0.53; P less than 0.0001). SmC concentrations after treatment were significantly lower in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.01), than in sham-operated animals and were elevated compared to those in sham-operated controls in the group receiving the lowest dose of EB (0.05 microgram; P less than 0.01). Posttreatment SmC levels correlated positively with delta GH (r = 0.58; P less than 0.001) and negatively with serum estradiol concentrations (r = -0.47; P less than 0.01). Pituitary glands from the remaining animals in each group (n = 4) were weighed and assayed for GH, PRL, and LH content. Pituitary PRL content increased with increasing doses of EB replacement and correlated strongly (r = 0.82; P less than 0.0001) with pituitary weight. In the castrated adult female rat, high doses of estrogen inhibited the GH secretory response to GRF in vivo and decreased SmC concentrations. Low dose estrogen increased SmC concentrations, although the GH secretary response to GRF in this group was similar to that in sham-operated rats. The latter observation suggests that the rise in SmC levels associated with low dose estrogen may not be mediated through a change in GH secretion.

The effect of the 44-amino-acid peptide human pancreatic GH releasing factor (hpGRF-44) upon the secretion of GH was studied in control and hypothyroid adult male rats. In animals rendered hypothyroid by ingestion of propylthiouracil (PTU), basal and hpGRF-44-stimulated secretion of GH was depressed in vivo. Administration of T4 together with PTU prevented the decline in basal and hpGRF-provoked GH secretion in vivo. HpGRF-44-stimulated release of rat GH was also impaired in vitro, an effect partially reversed by administration of low doses of T4 in vivo. The depressed in vitro secretion of GH could not be restored in hypothyroidism pituitaries by incubation of the glands with T3. Thus, hypothyroidism blunts hpGRF-44-stimulated secretion of GH in vivo and in vitro in the hypothyroid adult male rat.

Immunoreactive LRH (iLRH)-like material has been measured in extracts of urine from normal children and adolescents, adult men and women, and postmenopausal women. The urinary excretion of iLRH-like material was significantly greater in pubertal than in prepubertal subjects and in boys than girls at both stages of sexual maturation [prepubertal males, 3.26 +/- 0.49 ng/24 h (SE; n = 24); pubertal males, 5.94 +/- 1.36 (n = 12); prepubertal females, 1.14 +/- 0.21 (n = 19); pubertal females, 2.85 +/- 0.56 (n = 13)]. In adult males (n = 5) the urinary excretion of iLRH-like material was 7.8 +/- 1.3 ng/24 h, and in adult women in the follicular phase of the menstrual cycle (n = 8) it was 2.9 +/- 0.3. In five postmenopausal women the urinary iLRH-like content was 7.32 +/- 0.92 ng/24 h (P less than 0.01 relative to normal pubertal and adult women). In children the 24-h urinary excretion of iLRH-like material was positively correlated with chronological and bone ages, Tanner stage of genital (male) and breast (female) development, and the urinary excretion of LH and FSH in males. It did not correlate with the urinary excretion of either LH or FSH in females. Carboxymethylcellulose chromatography of extracts of urine from pubertal boys and girls, adult men and women, and postmenopausal women suggested that the iLRH-like material may be the 2-10 fragment of LRH rather than the intact decapeptide.