Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone
05 Jan 1973-Science (American Association for the Advancement of Science)-Vol. 179, Iss: 4068, pp 77-79
TL;DR: A peptide has been isolated from ovine hypothalamus which, at 1 x 10-9M, inhibits secretion in vitro of immunoreactive rat or human growth hormones and is similarly active in vivo in rats.
Abstract: A peptide has been isolated from ovine hypothalamus which, at 1 x 10(-9)M, inhibits secretion in vitro of immunoreactive rat or human growth hormones and is similarly active in vivo in rats. Its structure is H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH The synthetic replicate is biologically active.
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TL;DR: The purpose of this review is to provide a comprehensive survey of the current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.
Abstract: Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.
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TL;DR: Among the wide spectrum of SST effects, several biological responses have been identified that display absolute or relative subtype selectivity and selected nonpeptide agonists with nanomolar affinity have been developed.
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TL;DR: A 44 amino acid peptide with growth hormone-releasing activity has been isolated from a human tumor of the pancreas that had caused acromegaly and has full biological activity in vitro and in vivo specifically to stimulate the secretion of immunoreactive growth hormone.
Abstract: A 44 amino acid peptide with growth hormone-releasing activity has been isolated from a human tumor of the pancreas that had caused acromegaly. The primary structure of the tumor-derived peptide is H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser- Ala- Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Ar g-Gly -Ala-Arg-Ala-Arg-Leu-NH2. The synthetic replicate has full biological activity in vitro and in vivo specifically to stimulate the secretion of immunoreactive growth hormone. The tumor-derived peptide is identical in biological activity and similar in physiochemical properties to the still uncharacterized growth hormone-releasing factor present in extracts of hypothalamic tissues.
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TL;DR: In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF- I levels are normal.
Abstract: Since the original somatomedin hypothesis was conceived, a number of important discoveries have allowed investigators to modify the concept. Originally somatic growth was thought to be controlled by pituitary GH and mediated by circulating insulin-like growth factor-I (IGF-I, somatomedin C) expressed exclusively by the liver. With the discovery that IGF-I is produced by most, if not all, tissues, the role of autocrine/paracrine IGF-I vs. the circulating form has been hotly debated. Recent experiments using transgenic and gene-deletion technologies have attempted to answer these questions. In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF-I levels are normal. Thus, the normal postnatal growth and development in these animals may be due to normal free IGF-I levels (from as yet unidentified sources), although the role of autocrine/paracrine IGF-I has yet to be determined.
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Cites background from "Hypothalamic Polypeptide That Inhib..."
...Two hypothalamic factors, GH releasing hormone (GHRH) (75, 76) and the inhibitory hormone, somatostatin (SS) (77), act in concert to regulate GH secretion from pituitary somatotrophs....
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References
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TL;DR: The values of tryptophan obtained were close to the expected integral values and the recoveries of all other amino acids were comparable to those observed after hydrolysis with 6 n HCl.
993 citations
TL;DR: The sensitivity of the cultured cells to TRF and LRF is maintained for more than 2 weeks in culture although the magnitude of the secretory response and the intracellular hormone content declines with time in culture.
Abstract: A method for preparing short—term enzymatically dispersed pituitary cell cultures is described. It has been used to assay hypothalamic releasing factors. The cells secrete TSH or LH and FSH in amounts directly related to the dose of TRF or LRF respectively. The minimal active doses of synthetic TRF and either synthetic or highly purified ovine LRF is ca. 10-10M. Apparent affinity constants for TRF or LRF receptors are ca. 10-9M. Enhanced secretion rates of TSH or LH of 8– to 20–fold in response to maximal levels of TRF or LRF are routinely observed. The sensitivity of the cultured cells to TRF and LRF is maintained for more than 2 weeks in culture although the magnitude of the secretory response and the intracellular hormone content declines with time in culture. Chronic administration of TRF or LRF depletes the intracellular hormone levels while simultaneously increasing the total TSH or LH content in the culture (tissue and fluid). As has been observed with other in vitro systems, high medium potassium,...
524 citations
TL;DR: The primary structure of ovine hypothalamic hypophysiotropic luteinizing hormone-releasing factor, LRF, has been established as pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gel-NH(2) by hydrolysis of the peptide with chymotrypsin or pyrrolidone-carboxylylpeptidase and by analysis of the products by
Abstract: The primary structure of ovine hypothalamic hypophysiotropic luteinizing hormone-releasing factor, LRF, has been established as pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 by hydrolysis of the peptide with chymotrypsin or pyrrolidone-carboxylylpeptidase and by analysis of the products by an Edman-dansylation sequencing technique, as well as by mass spectrometry of the derived phenylthiohydantoins. A decapeptide with the proposed primary structure, prepared by total synthesis, gave the same result on sequencing. The synthetic decapeptide possesses the same biological activities as the native ovine LRF. The amino-acid sequence of ovine LRF is identical to that already published for porcine LRF.
436 citations
TL;DR: Male rat anterior pituitaries were incubated in vitro for 5 hr in Krebs-Ringer bicarbonate medium and the growth hormone (GH) released from the glands was estimated by the tibial epiphyseal cartilage assay.
Abstract: Male rat anterior pituitaries were incubated in vitro for 5 hr in Krebs-Ringer bicarbonate medium and the growth hormone (GH) released from the glands was estimated by the tibial epiphyseal cartilage assay. Addition of crude sheep or rat hypothalamic extract to the pituitaries increased the GH concentration in the medium on comparison to either diluent or cortical extract-treated controls. The ovine extracts also depleted pituitary GH concentration when injected into male rats in vivo. Gel filtration of either sheep or rat hypothalamic extract on a column of Sephadex G-25 resulted in the elution from the column of 2 zones which influenced the release of GH in vitro on addition to the incubated pituitaries. The first zone of activity to be eluted increased the release of GH from the glands severalfold, whereas the second zone inhibited the release of GH to levels about one half of that released by control glands incubated in the presence of the eluting buffer. Increasing the dose in the inhibitory zone res...
412 citations
TL;DR: Two analogs of the hypothalamic luteinizing hormone releasing factor modified at the histidine-2 position were tested for biological activity in cultures of dispersed rat anterior pituitary cells, and both analogs decrease the amount of luteInizing hormone secreted in response to the releasing factor.
Abstract: Two analogs of the hypothalamic luteinizing hormone releasing factor modified at the histidine-2 position were tested for biological activity (secretion of luteinizing hormone) in cultures of dispe...
120 citations