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Recent studies have demonstrated that passive immunization of neonatal rats to GRF inhibited their somatic growth through the suppression of GH secretion. In this study, we investigated the changes in pituitary GRF receptor (GRFR) expression in GRF antibody (GRF-ab) treated rats. Neonatal rats were treated from day 1 to day 10 after birth with every other day sc injection of 50 microliters of normal rabbit serum (groups I: control & III) or rabbit serum containing GRF-ab (groups II & IV). In addition, groups III & IV received twice daily injection of recombinant human GH (0.4 microgram/kg, sc). The rats were sacrificed on day 11 and pituitaries were removed. The pituitary weights in all treatment groups were decreased compared to the control group (I). Total pituitary RNA was extracted and GRFR mRNA levels were determined by RNase protection assay. Receptor RNA levels were quantitated and normalized to an internal standard, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The ratios of GRFR mRNA to GAPDH mRNA were significantly decreased to 49.6 +/- 4.9 (mean +/- SD), 73.0 +/- 8.7, 43.6 +/- 9.5% of control group I in the experimental groups II, III, and IV, respectively (P < 0.01). These data suggest that (1) suppression of GH secretion in GRF-ab treated animals was due, at least in part, to a decrease in GRFR expression, (2) GRF may be necessary for its own receptor expression, (3) exogenous administration of GH suppresses pituitary GRFR mRNA.

Growth hormone (GH)-releasing activity in plasma of normal or hypophysectomized male rats was investigated by the method of in vivo depletion of growth hormone in rat pituitaries. Plasma from rats hypophysectomized about 3 months previously depleted pituitary growth hormone when injected into the carotid artery of 40-day-old recipient rats. This activity was absent in plasma of rats hypophysectomized for only a week and from plasma of normal rats of the same age as the hypophysectomized rats. The GH-releasing activity of plasma from long-term hypophysectomized rats appeared to be of neural origin, since it was not present in aortic plasma 10 min after elimination of the cranial circulation. (Endocrinology 80: 77, 1967)

Pituitary FSH content following the intracarotid injection of pig and rat hypothalamic extracts was measured in normal, castrated, and castrated testosterone-treated adult male rats. Highly purified beef follicle-stimulating hormone releasing factor (FSH-RF) was also examined for its effect on release of pituitary FSH in castrated male rats pretreated with testosterone. No significant depletion of pituitary FSH was observed in normal adult male rats after administration of pig or rat hypothalamic extracts. In castrated male rats, pituitary FSH remained unchanged following the intracarotid injection of pig hypothalamic extracts [1.0 stalk median eminence (SME) /recipient animal] or rat hypothalamic extracts (2.0 SME/recipient animal). A significant depletion was obtained, however, in castrated male rats pretreated with testosterone propionate after administration ofeither pig or rat hypothalamic extracts (1–2 SME/recipient animal, respectively). Purified beef or pig FSH-RF also greatly depleted pituitary F...

Hypothalamic extracts from the dog, rabbit, mouse, kitten, pigeon, and frog were found to decrease the growth hormone (GH) content of rat pituitary glands. Comparable cerebral cortical extracts were completely inactive in this test. These results broaden previous observations on the existence of a GH-releasing factor (GRF) in the hypothalami of mammals and show the presence of GRF activity in birds and amphibians.

The influence of some central nervous system (CNS) active drugs on pituitary growth hormone (GH) content and on insulininduced GH release was investigated. GH was assayed by the “tibia test” method. Chlorpromazine (CPZ), reserpine and α-ethyltryptamine (Monase) were able to suppress the release of GH induced by 2 U/kg of insulin. High doses of reserpine induced GH release. Other CNS-active drugs, i.e., pentobarbital, morphine, desmethylimipramine, d-amphetamine and iproniazid, were unable to block the release of GH induced by insulin. Increase of pituitary GH was noticed after administration of D-amphetamine. The suppressive action of CPZ and reserpine appeared to be exerted on CNS and not on the pituitary, since rats pretreated with these drugs showed a normal depletion of pituitary GH content after administration of rat hypothalamic extracts. The block of insulin-induced GH release effected by CPZ, reserpine and Monase drugs with marked stressinhibitory activity suggested that insulin might act as a str...

Adult female rats in proestrus were given pentobarbital (Nembutal) in order to block spontaneous ovulation. Highly purified LH-releasing factor (LRF) was injected into their carotid arteries at different rates. Ten μg of this LRF, when injected over 30 min, induced full ovulation in all rats tested. One or 2 μg occasionally caused ovulation. One mg of an extract of pig cerebral cortex or 50 μg of FSH-releasing factor (FSH-RF) never did. Similar ovulatory responses were obtained when the LRF was injected quickly or over a 90-min period. On the other hand, LH induced ovulation more effectively when given by quick injection than when given slowly. LH induced ovulation in hypophysectomized animals, whereas our LRF did not. These results offer validation of a physiological effect induced by purified LRF preparation. (Endocrinology 80: 515, 1967)

Addition of small amounts of highly purified porcine growth hormone-releasing factor (GRF) to rat anterior pituitaries incubated in vitro for 6–24 hr in Krebs-Ringer bicarbonate media significantly increased the release of growth hormone (GH). This effect was abolished by actinomycin D. Although more GH was released in vitro under the influence of GRF, the GH content of pituitaries from normal rats exposed to GRF was essentially unchanged after the incubation. When the pituitaries of donor rats were depleted of GH by a prior exposure of rats to cold in vivo, GRF was shown to stimulate the synthesis of GH in the incubated tissue as well as the release of GH. The results lend support to the thesis that one substance is responsible for both the release and synthesis of GH. (Endocrinology 82: 271, 1968)

Acetic acid extracts of bovine hypothalamic tissue were concentrated by a precipitation procedure and subjected to gel filtration on Sephadex. Follicle-stimulating hormone- releasing factor (FSH-RF) activity was followed by measuring depletion of follicle-stimulating hormone (FSH) from pituitaries of normal, or castrated testosterone-treated male rats, as well as elevation of plasma FSH activity in castrated female rats treated with estrogen and progesterone. FSH-RF activity was found consistently to emerge from Sephadex just after β-MSH and before luteinizing hormone-releasing factor (LRF) and vasopressin. Bovine FSH-RF purified by gel filtration on Sephadex is essentially free of LRF. The LRF active fractions from Sephadex do not show any FSH-RF activity. The FSH-RF zone from Sephadex was further purified by phenol extraction and then chromatographed on carboxymethylcellulose (CMC). This step separated FSH-RF from thyrotropic hormone-releasing factor (TRF). Purified FSH-RF was active in vivo at the leve...

SummaryExperiments were performed in the rat to determine whether the increased secretion of growth hormone (GH) during stress involves augmentation of synthesis and/or release of hypothalamlc GH-releasing factor (GRF). Two different stimuli were used as stress: injection of formalin, which was previously shown to be ineffective in inducing GH release; and cold exposure, which evoked depletion of pituitary GH. Exposure of rats to cold (4°C) for 1 hr resulted in a significant depletion of pituitary GH, which was accompanied by disappearance of hypothalamic GRF and appearance of GRF activity in plasma. Cold exposure for 5 minutes was ineffective. Injection of 10% formalin did not induce pituitary GH depletion, or affect hypothalamic and plasma GRF activity. These results indicate that some stressful stimuli, such as cold exposure, capable of releasing GH, induce this effect via the hypothalamus; other stresses, like formalin injection, which do not release GH, exert little effect on the GH-release mechanism...

Highly purified pig LH-releasing factor (LRF) was tested for the ability to inhibit pituitary prolactin secretion in vivo (PIF activity). Cervical stimulation induced a significant depletion of pituitary prolactin content in estrous rats. When extract equivalent to 1 fragment of pig stalk median eminence was given before the stimulation, the depletion of pituitary prolactin was completely blocked. On the other hand, pretreatment with 50 μg of purified LRF, equivalent to 300 fragments of pig SME, failed to block the prolactin depletion following cervical stimulation. Pork LRF used in these studies raised plasma LH in ovariectomized rats pretreated with estrogen and progesterone in as small a dose as 0.05 μg. One μg LRF also induced ovulation in Nembutal-blocked cyclic rats. Thus, highly purified pork LRF was clearly devoid of PIF activity. This supports our previous conclusion that LRF is different from PIF. (Endocrinology 80: 972, 1967)