Structure of porcine thyrotropin-releasing hormone

Nair, R. M. G.; Barrett, John; Bowers, Cyril Y.; Schally, Andrew V.

doi:10.1021/bi00807a008

Cited by 199 publications

(39 citation statements)

References 22 publications

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“…A similar relationship has already been shown to exist in the case of the hypothalamic thyrotropin releasing factors of ovine and porcine origin, both of which have the amino-acid sequence pGlu-His-Pro-NH2 (27)(28)(29). Of considerable physiological interest is the observation (12,14,30) that synthetic LRF stimulates the secretion of both luteinizing and follicle-stimulating hormones, thus reducing the probability that the follicle-stimulating hormone released by native LRF might have been due to a contaminant.…”

Section: Discussionsupporting

confidence: 66%

Primary Structure of the Ovine Hypothalamic Luteinizing Hormone-Releasing Factor (LRF)

Burgus¹,

Butcher²,

Amoss³

et al. 1972

Proc. Natl. Acad. Sci. U.S.A.

444

150

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The primary structure of ovine hypothalamic hypophysiotropic luteinizing hormone-releasing factor, LRF, has been established as pGlu-His-Trp-SerTyr-Gly-Leu-Arg-Pro-Gly-NH2 by hydrolysis of the peptide with chymotrypsin or pyrrolidone-earboxylylpeptidase 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.Various areas of the central nervous system participate in the fine regulation of the secretion of all adenohypophysial hormones. The ultimate integrator of information originating in the central nervous system is the hypothalamus. The final information from the hypothalamus to the adenohypophysis is not transmitted in the form of nerve impulses, but is carried in the form of specific hypothalamic hypophysiotropic substances, the hypothalamic releasing factors, that are carried through the hypothalamo-hypophysial portal system of capillaries from the median eminence region of the ventral hypothalamus to the cells of the adenohypophysis. There is good physiological evidence that such a hypothalamic control is involved in the secretion of the gonadotropin, luteinizing hormone. In the early 1960s, several investigators reported experimental results that were best explained by proposing the existence of substances that specifically stimulated the secretion of luteinizing hormone, and that were probably polypeptides, in crude aqueous extracts of hypothalamic tissues of various mammalian species (1-3). Preparations of LRF, active at 1 /Ag per dose in animal bioassays, were obtained by gel filtration and ion-exchange chromatography on carboxymethylcellulose (4), an observation that was confirmed by similar methods by several investigators (5, 6). In spite of the vagaries of the various bioassay methods available, several laboratories reported preparations of LRF of increased potency (5, 6). Several of these early publications led to contradictory statements regarding purification and separation of LH-releasing factor (LRF), from a follicle-stimulating hormone releasing factor (5, 7). Two laboratories independently reported the isolation of porcine LRF (8) and ovine LRF (9), both groups concluding that LRF from either species was a nonapeptide containing, on the basis of acid hydrolysis, 1 His, 1 Arg, 1 Ser, 1 Glu, 1 Pro, 2 Gly, 1 Leu, 1 Tyr. Earlier results with the pyrrolidone-carboxylylpeptidase prepared by Fellows and Mudge (10) had led us to conclude (11) that the Nterminal residue of LRF was Glu in its cyclized pyroglutamic (pGlu) form, as in the case of hypothalamic TRF, (pGluHis-Pro-NH2).While our own studies on the amino-acid sequence of ovine LRF were in progress, Matsuo et al. (12) reported that porcine LRF contai...

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Section: Discussionsupporting

confidence: 66%

Primary Structure of the Ovine Hypothalamic Luteinizing Hormone-Releasing Factor (LRF)

Burgus¹,

Butcher²,

Amoss³

et al. 1972

Proc. Natl. Acad. Sci. U.S.A.

444

150

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“…Since the initial isolation of TRH from the hypothalamus (3,21) it has become evident that this tripeptidke is distributed throughout the extrahypothalamic central nervous system (CNS) and spinal cord (2,16,24).…”

Section: Discussionmentioning

confidence: 99%

Respiratory Effects of TRH in Preterm Rabbits

Hedner¹,

Hedner²,

Jonason³

et al. 1982

Pediatr Res

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SummaryThe respiratory activity in newborn preterm (29 days gestation) rabbits was studied after administration of thyrotropic releasing hormone. Intraperitoneal injection induced an increase in respiratory frequency (f) and a decrease in tidal volume (VT) resulting in a slight increase in pulmonary ventilation (VE). These effects were seen in parallel to a decrease in expiratory time (TE) and respiratory time (TToT). An increase in the TI/TTOT ratio but (unaffected) VT/TI ratio indicates that thyrotropic releasing hormone affects "respiratory timing" mechanisms rather than "inspiratory drive." The changes in respiratory parameters are most probably due to an effect on the central respiratory controlling centers in the brain stem.

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“…Five families of hypothalamic neuropeptides involved in the control of anterior pituitary hormone secretion have now been characterized, namely, thyrotropin-releasing hormone (3,4), gonadotropinreleasing hormone (5), somatostatin (6), corticotropinreleasing hormone (7), and growth hormone-releasing hormone (8,9). Early experimental observations have demonstrated that the intermediate lobe of the pituitary is under hypothalamic inhibitory control (10,11), and dopamine has been shown to play a pivotal role in the negative regulation of pituitary melanotrophs (12,13).…”

mentioning

confidence: 99%

Characterization of melanotropin-release-inhibiting factor (melanostatin) from frog brain: homology with human neuropeptide Y.

Chartrel¹,

Conlon²,

Danger³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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A polypeptide was purified from frog brain extracts on the basis of its ability to inhibit a-melanotropin release from perifused frog neurointermediate lobes. Based on Edman degradation, amino acid analysis, and peptide mapping, the primary structure of this frog melanotropin-releaseinhibiting factor (melanostatin) was determined to be H-TyrPro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala-Pro-Ala-GluAsp-Met-Ala-Lys-Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile-AsnLeu-Ile-Thr-Arg-Gln-Arg-Tyr-NH2. Frog melanostatin belongs to the pancreatic polypeptide/neuropeptide Y/peptide YY family, and the structure of this peptide differs from that of human neuropeptide Y by only one amino acid substitution in position 19. A synthetic replicate of frog melanostatin is coeluted with the native peptide on HPLC and is highly potent in inhibiting a-melanotropin secretion in vitro (IC50 = 60 nM).Both the anterior lobe and the intermediate lobe of the pituitary are regulated by hypophysiotropic factors originating from the hypothalamus (1, 2). Five families of hypothalamic neuropeptides involved in the control of anterior pituitary hormone secretion have now been characterized, namely, thyrotropin-releasing hormone (3, 4), gonadotropinreleasing hormone (5), somatostatin (6), corticotropinreleasing hormone (7), and growth hormone-releasing hormone (8,9 (20)(21)(22). However, many studies failed to demonstrate that these peptides meet the criteria expected of a physiological melanotropin-release-inhibiting factor (melanostatin) (23)(24)(25). We report here the purification, sequence analysis, and total synthesis of a 36-residue peptide that is highly potent in inhibiting the secretion of a-melanotropin from frog neurointermediate lobe in vitro. MATERIALS AND METHODSPurification Procedure. Adult frogs (Rana ridibunda) were obtained from a commercial source (Coudtard, St-Hilaire de Riez, France). The brains from 1200 animals (94.5 g, wet weight) were collected on dry ice and kept frozen. The tissue was boiled for 15 min in 0.5 M acetic acid and homogenized in a Waring blendor. After centrifugation (10,000 x g for 30 min at 40C), the supernatant was pumped at a flow rate of 2 ml/min through ten Sep-Pak C18 cartridges (Waters Associates) connected in series. Bound material was eluted with 70% (vol/vol) acetonitrile in water and lyophilized. The dry extract was dissolved in 10 ml of 1% (vol/vol) trifluoroacetic acid and chromatographed on a 2.5 x 100-cm column of Sephacryl S-100 (Pharmacia-LKB) equilibrated with 1 M acetic acid at a flow rate of 2 ml/min. Fractions (10 ml) were collected and absorbance was measured at 280 nm (Fig. 1A).The fractions exhibiting melanotropin-release-inhibiting activity were pooled and 50% of the total material was analyzed by HPLC.The active fraction was pumped at a flow rate of 2 ml/min onto a 1 x 25-cm Vydac 218 TP510 C18 column (The Separations Group) equilibrated with 0.1% trifluoroacetic acid and eluted at a flow rate of 2 ml/min, using the gradient indicated in Fig. 1B. Absorbance was measured at 214 and 280 ...

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Structure of porcine thyrotropin-releasing hormone

Cited by 199 publications

References 22 publications

Primary Structure of the Ovine Hypothalamic Luteinizing Hormone-Releasing Factor (LRF)

Primary Structure of the Ovine Hypothalamic Luteinizing Hormone-Releasing Factor (LRF)

Respiratory Effects of TRH in Preterm Rabbits

Characterization of melanotropin-release-inhibiting factor (melanostatin) from frog brain: homology with human neuropeptide Y.

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