Human Placental Lactogen Decreases Regional Blood Flow in Anesthetized Pigs

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Abstract

In 22 pigs anesthetized with sodium pentobarbitone, changes in blood flow caused by infusion of human placental lactogen into the left renal, external iliac, and anterior descending coronary arteries were assessed using electromagnetic flowmeters. In 17 pigs, infusion of human placental lactogen whilst keeping the heart rate and arterial pressure constant decreased coronary, renal and iliac flow. In 5 additional pigs, increasing the dose of human placental lactogen produced a dose-related decrease in regional blood flow. The mechanisms of the above response were studied in 15 of the 17 pigs by repeating the experiment of infusion. The human placental lactogen-induced decrease in regional blood flow was not affected by blockade of cholinergic receptors (5 pigs) or of α-adrenergic receptors (5 pigs), but it was abolished by blockade of β<sub>2</sub>-adrenergic receptors (5 pigs). The present study showed that intra-arterial infusion of human placental lactogen primarily decreased coronary, renal and iliac blood flow. The mechanism of this response was shown to be due to the inhibition of a vasodilatory β<sub>2</sub>-adrenergic receptor-mediated effect.

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Most cited references 23

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Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis.

Víctor Martínez, Ana M. Corbacho, C Clapp (2002)

Prolactin, growth hormone and placental lactogen are members of a family of polypeptide hormones which share structural similarities and biological activities. Numerous functions have been attributed to these hormones, among which stand out their recently discovered effects on angiogenesis, the process by which new blood vessels are formed from the pre-existing microvasculature. Prolactin, growth hormone and placental lactogen, along with two non-classical members of the family, proliferin and proliferin-related protein, can act both as circulating hormones and as paracrine/autocrine factors to either stimulate or inhibit various stages of the formation and remodeling of new blood vessels, including endothelial cell proliferation, migration, protease production and apoptosis. Such opposing actions can reside in similar but independent molecules, as is the case of proliferin and proliferin-related protein, which stimulate and inhibit angiogenesis respectively. The potential to exert opposing effects on angiogenesis can also reside within the same molecule as the parent protein can promote angiogenesis (i.e. prolactin, growth hormone and placental lactogen), but after proteolytic processing the resulting peptide fragment acquires anti-angiogenic properties (i.e. 16 kDa prolactin, 16 kDa growth hormone and 16 kDa placental lactogen). The unique properties of the peptide fragments versus the full-length molecules, the regulation of the protease responsible for specific protein cleavage, the selective expression of specific receptors and their associated signal transduction pathways are issues that are being investigated to further establish the precise contribution of these hormones to angiogenesis under both physiological and pathological situations. In this review article, we summarize the known and speculative issues underlying the effects of the prolactin, growth hormone and placental lactogen family of proteins on angiogenesis, and address important remaining enigmas in this field of research.

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Variation among species in the endocrine control of mammary growth and function: the roles of prolactin, growth hormone, and placental lactogen.

P A Forsyth (1986)

Prolactin, growth hormone, and placental lactogen form a family of structurally related hormones, which may have evolved from a common ancestral peptide. Prolactin and growth hormone are present in all mammals, but the biological activity associated with placental lactogen has been detected in only some groups. Attempts to detect placental lactogen using bioassay and radioreceptor assay are reported and have been unsuccessful in an insectivore (the shrew), a bat, an edentate (the armadillo), a lagomorph (the rabbit), several carnivores (dog, cat, ferret), perissodactyls (horse, zebra, rhino), and, within the artiodactyls, pigs. Placental lactogenic activity has been detected in primates (chimpanzee, orangutan), rodents (voles, Pinon mouse, guinea-pig, mara), and in numerous artiodactyls (llama, giraffe, several species of deer, antelope, gnu, gazelle, musk ox, cape buffalo, Barbary sheep, several sheep of the genus Ovis, goat, and cow). These results confirm and extend the work of others and are discussed in relation to the evolution of these hormones. In synergism with steroid and thyroid hormones, protein hormones of the prolactin and growth hormone family play a crucial role in stimulating the development of the mammary gland, the differentiation and function of mammary cells to secrete milk, and in the systemic adjustments in maternal metabolism in pregnancy and lactation. Studies in vitro have shown that mammary tissues from several species synthesize milk components in response to insulin plus adrenal corticoid plus prolactin. However, there are also species differences in minimal hormonal requirements for lactogenesis. In vivo, for example, rabbits will initiate or sustain lactation in response to prolactin alone, whereas sheep and goats require prolactin plus growth hormone plus adrenal corticoid plus thyroid hormone. Measurement of hormone concentrations in the plasma of pregnant animals shows considerable differences among species in the pattern of secretion of lactogenic hormones to bring about mammary development. A surge of prolactin secretion occurs at parturition but may not be essential in the initiation of lactation. The timing of progesterone withdrawal correlates well with lactogenesis in eutherian mammals, but species differ in the mechanisms at parturition which bring this about. Marsupials show a quite different pattern of suckling-induced lactation. In maintaining lactation the greatest contrast is between ruminants, in which growth hormone is of particular importance, and other mammals, in which reduction of prolactin secretion with bromocriptine rapidly suppresses milk synthesis and secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

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The effect of testosterone on regional blood flow in prepubertal anaesthetized pigs.

Mario A. Battaglia, G Vacca, C. Molinari … (2002)

This work was undertaken to study the effects of testosterone on the coronary, mesenteric, renal and iliac circulations and to determine the mechanisms of action involved. In prepubertal pigs of both sexes anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary, superior mesenteric, left renal and left external iliac blood flow caused by intra-arterial infusion of testosterone were assessed using electromagnetic flowmeters. Changes in heart rate and arterial blood pressure were prevented by atrial pacing and by connecting the arterial system to a pressurized reservoir containing Ringer solution. In 12 pigs, intra-arterial infusion of testosterone for 5 min to achieve a stable intra-arterial concentration of 1 microg l(-1) increased coronary, mesenteric, renal and iliac blood flow without affecting the maximum rate of change of left ventricular systolic pressure (left ventricular dP/dt(max)) and filling pressures of the heart. In a further five pigs, a concentration-response curve was obtained by graded increases in the intra-arterial concentration of the hormone between 0.125 and 8 microg l(-1). The mechanisms of these responses were studied in the 12 pigs by repeating the experiment after haemodynamic variables had returned to the control values before infusions. In six pigs, blockade of muscarinic cholinoceptors and adrenoceptors with atropine, propranolol and phentolamine did not affect the responses caused by intra-arterial infusion of testosterone performed to achieve a stable intra-arterial concentration of 1 microg l(-1). In the same pigs and in the remaining six pigs, the increases in coronary, mesenteric, renal and iliac blood flow caused by intra-arterial infusion of testosterone performed to achieve a stable intra-arterial concentration of 1 microg l(-1) were prevented by intra-arterial injection of N(omega)-nitro-L-arginine methyl ester. The present study shows that intra-arterial infusion of testosterone dilated coronary, mesenteric, renal and iliac circulations. The mechanism of this response involved the release of nitric oxide.

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Author and article information

Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 2006

Publication date (Print): February 2006

Publication date (Electronic): 16 February 2006

Volume: 43

Issue: 2

Pages: 205-213

Affiliations

Laboratorio di Fisiologia, Dipartimento di Scienze Mediche, Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale ‘A. Avogadro’, Novara, Italy

Article

Publisher ID: 90950 Other ID: J Vasc Res 2006;43:205–213

DOI: 10.1159/000090950

PubMed ID: 16410683

SO-VID: 56782bf5-17a5-4fd2-ac05-f8caaa7ff24b

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 14 June 2005

Date accepted : 02 November 2005

Page count

Figures: 4, Tables: 1, References: 34, Pages: 9

Human Placental Lactogen Decreases Regional Blood Flow in Anesthetized Pigs

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Karger: Cardiovascular System

Most cited references 23

Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis.

Variation among species in the endocrine control of mammary growth and function: the roles of prolactin, growth hormone, and placental lactogen.

The effect of testosterone on regional blood flow in prepubertal anaesthetized pigs.

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