Further Observations on the Intermediate Lobe Pituitary Hormone

Landgrebe, F. W.; Reid, E.; Waring, H.

doi:10.1113/expphysiol.1943.sp000880

Cited by 30 publications

(4 citation statements)

References 3 publications

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“…Apparently, however, the intensity of the hyperglycaemia is dependent on some additional factor, as the bloodsugar level was higher after thyroxine treatment in the summer than in spring and autumn. It was thought that variation in the amount of circulating melanophoreexpanding hormone might be responsible for this difference [Landgrebe, Reid & Waring, 1944], but adaptation to a light back-ground for 4-6 days provided no experimental support for such a thesis. Neither is the variation in response related to the glycogen content of the liver, as this is much higher in October than in the summer months.…”

Section: Discussionmentioning

confidence: 98%

The Relation Between Seasonal Hyperglycaemia and Thyroid Activity in the Frog (Rana Temporaria)

Smith¹

1954

Journal of Endocrinology

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The mean blood-sugar level of frogs killed in the field without previous excitement showed no significant variation between April and October inclusive (38\m=+-\1\m=.\42mg/100 ml.). The resting blood-sugar level at other times of the year, after 2-3 days in captivity, was slightly lower.A marked hyperglycaemic response to excitement could be elicited in the majority of frogs at the spawning season (March) and throughout the summer, while it was only found in April and early May in a few frogs which showed early development of the gonadial fat-bodies. The response was much reduced in September and absent in October.The seasonal occurrence of the hyperglycaemic response paralleled the known cycle of thyroid activity, and a significant correlation was found between the blood-sugar level and thyroid condition in individual excited frogs. A significant response to excitement has been induced in spring, summer and autumn by previous treatment with thyroxine. It is suggested that the thyroid hormone inhibits the destruction of circulating adrenergic compounds.The role of temperature in limiting the hyperglycaemic response is discussed.In an earlier paper [Smith, 1950] attention was drawn to a seasonal variation in the blood-sugar level of frogs (Rana temporaria) which had been in captivity and unfed for 72 hr. In the course of subsequent work, it became apparent that at some seasons the frog showed a marked hyperglycaemic response to handling and shaminjection. This made a re-investigation of seasonal resting blood-sugar levels desirable. At the same time the response to excitement was studied, and in several experiments thyroxine was given in an attempt to induce hyperglycaemia in unresponsive animals. MATERIAL AND METHODSThe majority of the frogs used for the seasonal work were collected in the Wirral Peninsula. In the early months of the year it was not possible to find frogs locally, and they were obtained from a dealer in Staffordshire. These animals were received on the day following their capture and were at once put in a large glass-sided slate tank at approximately atmospheric temperature. Such frogs were not used until they had been in their new surroundings for 24 hr. The frogs used for the experimental induction of hyperglycaemia were all obtained from the dealer and were kept under similar conditions, except that in some cases they were at room temperature (17-20°C), and not at atmospheric temperature (9-11°C). The frogs were not fed while in captivity. Excited and unexcited frogs Frogs which have been termed ' unexcited ' were either freshly caught, or, in the case of already captive animals, were removed from the tank with minimal disturbance and killed immediately. Blood samples from freshly caught, unexcited frogs were

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Section: Discussionmentioning

confidence: 98%

The Relation Between Seasonal Hyperglycaemia and Thyroid Activity in the Frog (Rana Temporaria)

Smith¹

1954

Journal of Endocrinology

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“…Such changes in biological effects have been discussed in terms of "potentiation," "prolongation," and "retardation" (7)(8)(9)(10)(11)(12). Although the precise biochemical mechanism by which these unusual biological properties were produced is unknown, it appeared possible that synthetic stereostructural tailoring of a-MSH might produce an analogue that would also possess these properties.…”

mentioning

confidence: 99%

4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity.

Sawyer

Sanfilippo

Hruby

et al. 1980

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

521

426

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ABSTRACTa-Melanocyte-stimulating hormone (a-MSH) reversibly darkens frog skins by stimulating melanosome movement (dispersion) within melanophores. Heat-alkali treatment of a-MSH results in prolonged biological activity of the hormone. Quantitative gas chromatographic analysis of the hydrolyzed heat-alkali-treated peptide revealed partial racemization particularly at the 4 (methionine) and 7(phenylalanine) a-Melanotropin (a-MSH, a-melanocyte-stimulating hormone) is a tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-ArgTrp-Gly-Lys-Pro-Val-NH2) that is synthesized and secreted by the pars intermedia of the vertebrate pituitary (1). The amino acid residues that are important in the expression of melanotropic activity have been elucidated through systematic structure-function investigations of a-MSH and a-MSH fragments on amphibian melanophores (2, 3) and, to a lesser extent, on mammalian melanoma cells (4-6). Very little information is available, however, regarding the stereochemical and conformational correlates of biological activity in either of these two biological systems.Earlier reports have shown that heat-alkali treatment of crude or purified preparations of naturally occurring a-MSH produces a partially racemized product with altered activity on amphibian melanophores both in vivo and in vitro. Such changes in biological effects have been discussed in terms of "potentiation," "prolongation," and "retardation" (7-12). Although the precise biochemical mechanism by which these unusual biological properties were produced is unknown, it appeared possible that synthetic stereostructural tailoring of a-MSH might produce an analogue that would also possess these properties. Utilizing a high-resolution gas chromatographic method to localize and quantitate specific sites of racemization within the primary sequences of peptides, we obtained additional evidence which suggested that stereochemical substitution at position 7 (replacement of L-phenylalanine by D-phenylalanine) of a-MSH or [Nle4]-a-MSH would provide an analogue with the desired biological properties. Previous investigations have shown that [Nle4]-a-MSH is more potent than a-MSH on both amphibian melanophores (2, 6) and on stimulating melanoma adenylate cyclase (6, 13), and it is also resistant to inactivation by chloramine-T (14, 15), an oxidant used in peptide iodination. Because heat-alkali treatment of this analogue also resulted in "potentiation," "prolongation," and "retardation," it was clear that alteration of the methionine residue was not a requirement for the expression of these properties. Thus, it was decided to retain the benefits of the norleucine substitution in position 4 in the synthesis of the "definitive" peptide.We report here the synthesis of [Nle4, D-Phe7]-a-MSH and present data demonstrating its unique biological properties. These include prolonged biological activity, enhanced potency relative to a-MSH in a number of biological systems, and resistance to degradation by serum enzymes. The biological properties of this analogue provide...

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“…In previous investigations Jores (1933), Holmquist (1934) and Jores 8c Beck (1934) found a hypertrophy of the adrenal cortex in intact rabbits, guinea pigs and rats after treatment with intermedin, but recently Karkun et al (1953), who reinvestigated these experiments with an intermedin prepared from pos¬ terior lobe powder by the same method (Landgrebe et al, 1944), as used by de Wied 8c Gaarenstroom (1953) were unable to confirm the statements of these previous authors, since no change in the adrenal cortex was evoked.…”

Section: Discussionmentioning

confidence: 97%

Melanophore Reaction and Adrenocorticotrophic Hormone

Thing

1954

Acta Endocrinologica

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The physiological role of intermedin, the melanophore expanding hormone (ME) in mammals is still unexplained.Since the reports of Sprague et al. (1950), Johnsson & H\l=o"\gberg(1952) and Sulman (1952), in which it was established that ACTH injected into frogs produced a darkening of the skin, caused by a melanophore reaction, the hormone has received a new and topical interest. It was suggested that intermedin and ACTH were closely related chemically or identical, and that assay of melanophore expansion activity in the frog could be employed as a convenient test for ACTH.

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Further Observations on the Intermediate Lobe Pituitary Hormone

Cited by 30 publications

References 3 publications

The Relation Between Seasonal Hyperglycaemia and Thyroid Activity in the Frog (Rana Temporaria)

The Relation Between Seasonal Hyperglycaemia and Thyroid Activity in the Frog (Rana Temporaria)

4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity.

Melanophore Reaction and Adrenocorticotrophic Hormone

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