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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 2 607-610
Copyright © 1997 by The Endocrine Society

Clinical Studies

Effects of Ovine Corticotropin-Releasing Hormone Injection and Desmopressin Coadministration on Galanin and Adrenocorticotropin Plasma Levels in Normal Women

Graziano Ceresini, Marilena Freddi, Piero Paccotti, Giorgio Valenti and Istvan Merchenthaler

Chair of Geriatrics (G.C., M.F., G.V.), University of Parma, Parma; and the Department of Internal Medicine (P.P.), University of Torino, Torino, Italy; and Wyeth-Ayerst Research (I.M.), Radnor, Pennsylvania 19087

Address all correspondence and requests for reprints to: Dr. Graziano Ceresini, Chair of Geriatrics, University of Parma, Via don Bosco 2, 43100 Parma, Italy.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
The neuropeptide galanin (GAL) has been shown to be located in the pituitary gland and to modulate the secretion of several pituitary hormones. In the human pituitary, GAL is almost exclusively located within corticotrophs. We examined whether GAL is secreted from corticotrophs in response to stimuli that induce ACTH release. Plasma levels of GAL and ACTH were evaluated in six healthy female subjects in the follicular phase of the menstrual cycle after the following treatments: 1) ovine CRH (oCRH) injection during saline (SAL) infusion, 2) oCRH injection during infusion of the arginine vasopressin analog desmopressin (DP), 3) SAL injection during DP infusion, and 4) SAL injection during SAL infusion. DP (4.3 ng/min·kg BW) or SAL was infused from 0–60 min. oCRH (1 µg/kg BW) or SAL was administered by a 2-min injection at 5 min.

The expected ACTH response to oCRH was enhanced by the concomitant DP administration (peak level, 10.39 ± 1.12 vs. 21.37 ± 3.43 pmol/L in SAL infusion plus oCRH injection vs. DP infusion plus oCRH injection, respectively; P < 0.05). The mean integrated ACTH response, expressed as the area under the curve, to SAL infusion plus oCRH injection vs. that to DP infusion plus oCRH injection was 288.23 ± 61.94 vs. 699.70 ± 91.80 pmol/L·60 min, respectively (P < 0.05). A slight, but not significant, increase was observed in ACTH values after DP infusion plus SAL injection compared to that after SAL infusion plus SAL injection challenge. Plasma GAL levels were highly variable. No changes in GAL levels were found concomitant to ACTH values in either experimental group. In fact, GAL levels were not significantly affected by either treatment. These data confirm that DP potentiates the ACTH response to CRH in humans. Furthermore, our results suggest that GAL is probably not cosecreted with ACTH in normal subjects. The possibility exists that GAL produced by corticotrophs exerts its action principally through a locally mediated paracrine or autocrine mechanism without being secreted into the bloodstream.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
GALANIN (GAL) is a 29 (30 in humans)-amino acid neuropeptide originally isolated from porcine intestine and subsequently found to be widely distributed in both central and peripheral nervous systems, the respiratory and genito-urinary tracts, the pituitary gland, and many other endocrine tissues (1–3; for review, see Ref.4). Although GAL regulates PRL, gonadotropin, and GH secretion (5, 6) in the rat pituitary, it only affects GH secretion in humans (7, 8). GAL-like immunoreactivity has been detected in lactotrophs, thyrotrophs, and somatotrophs (9), but appears to be confined to corticotrophs in humans (10). These morphological findings have been confirmed in both normal and adenomatous pituitary samples (10). Moreover, in situ hybridization histochemical studies have shown GAL messenger ribonucleic acid in ACTH-containing cells of human pituitary (11). These observations indicate a close relationship between the expression and secretion of GAL and ACTH (11) and raise a question about the role played by GAL produced by corticotrophs in human physiology. One possibility is that GAL is cosecreted with ACTH under stimuli exerted on corticotrophs. The major hypothalamic secretagogues for ACTH release in humans are CRH and arginine vasopressin (AVP) (12). The AVP analog (1-deamino-8-arginine vasopressin; dDAVP) desmopressin (DP), although ineffective on basal ACTH levels, has been recently shown to potentiate CRH-induced ACTH secretion in humans (13). With these premises, we evaluated the concomitant circulating levels of GAL and ACTH after the administration of ovine CRH (oCRH), DP, or the combination of the two peptides in normal human female subjects.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Six regularly menstruating women, aged 28.8 ± 0.7 yr, with a mean body mass index of 20.96 ± 0.7%, were studied in the follicular phase of the menstrual cycle. None of the subjects had a history of physical or psychiatric illnesses. The subjects were enrolled after a complete clinical and laboratory examination and were not currently smoking or taking medication. Caffeine intake was low in each subject.

All subjects gave informed consent to the study. The protocol was approved by the local ethical committee of the University of Parma.

Study design

The subjects were studied according to a randomized, single blind design in which four tests were performed in each subject. The tests were made between days 6–10 of the follicular phase of four consecutive menstrual cycles.

All tests were performed in the morning after an overnight fast. At 0830 h, an iv cannula was inserted into the anterior cubital vein of each arm and kept patent with a slow saline (0.9% NaCl; SAL) infusion. After a 30-min period, the subjects were challenged by the following treatments in random order: 1) iv infusion of SAL (100 mL) from 0–60 min plus oCRH, dissolved in 2 mL SAL (slow 2-min bolus injection; 1 µg/kg BW) at 5 min (INALCO, Milan, Italy); 2) iv infusion of SAL (see above) plus SAL (2 mL; slow 2-min bolus injection) at 5 min; 3) iv infusion of DP (Minirin dDAVP, Valeas, Milan, Italy; 4.3 ng/kg·min, dissolved in 100 mL SAL) from 0–60 min plus oCRH injection (see above); and 4) iv infusion of DP (see above) plus SAL injection (see above). The time of the beginning of either SAL or DP infusions was denoted 0 min. Blood was withdrawn at -30, 0, 10, 20, 30, 45, and 60 min from the beginning of SAL or DP infusions and collected in chilled polypropylene tubes containing ethylenediamine tetraacetate (1 mg/mL blood) and aprotinin (500 kallikrein inhibitor units/mL blood). Blood samples were kept on ice and immediately centrifuged for plasma separation. Plasma was stored at -80 C for ACTH and GAL evaluations. The bolus injections of oCRH or SAL as well as blood collection were performed through the iv cannula positioned in the arm contralateral to the one in which DP or SAL was infused. Systolic (SBP) and diastolic (DBP) blood pressure levels were measured by a sphygmomanometer and recorded together with heart rate (HR) at 0, 20, 30, 45, and 60 min. All tests were performed in a quiet, temperature-controlled (21 C) room. Side-effects of the treatments were recorded throughout each test by a researcher blinded to the content of the infusion or injection.

Peptide assay

Immunoreactive ACTH levels were determined in duplicate in unextracted plasma by an immunoradiometric assay, using a commercial kit (Nichols Institute, San Juan Capistrano, CA) and monoclonal antibodies directed at the ACTH-(1–17) sequence. The sensitivity of the method was 0.22 pmol/L. Intra- and interassay coefficients of variations at 4.4 pmol/L (n = 5) were 4.9% and 8.1%, respectively.

Plasma samples (1 mL) for GAL evaluations were extracted in 1% trifluoroacetic acid and 60% acetonitrile, using Sep-column C18 reverse phase cartridges (Peninsula, Belmont, CA). After extraction, the samples were dried in a vacuum centrifuge and resuspended in phosphate buffer (pH 7.4). GAL levels were determined by RIA, using kits from Peninsula with a sensitivity of 0.77 pmol/L, an ED50 of 34.87 pmol/L, and an IC80 of 9.3 pmol/L. The rabbit antihuman GAL antiserum had 100% cross-reactivity with both rat and porcine GALs, but no cross-reactivity with porcine GAL message-associated peptide, substance P, human vasoactive intestinal polypeptide, or human secretin (data from Peninsula). Each measurement was performed in duplicate, with a mean recovery of 72.8%. The intra- and interassay coefficients of variation were 10.9% and 12.9%, respectively, at 1.58 pmol/L (n = 5) and 11.3% and 12.5%, respectively, at 22.10 pmol/L (n = 5).

Statistical analyses

The results were compared within each group using the Friedman rank test, followed by the Wilcoxon rank signed test to identify individual differences between means. When significantly increased above baseline, secretory responses to stimulations were also evaluated as the integrated area under the curve (AUC), determined by the trapezoidal rule after subtracting the basal values (mean of -30 and 0 values). The above-described tests were also used to compare the AUC values. All statistical calculations were made using SPSS software (SPSS, Chicago, IL) (14). Statistical significance was defined as P < 0.05. The values are expressed as the mean ± SE.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Plasma ACTH levels in the four different tests are shown in Fig. 1Go. After the oCRH stimulus, administered during SAL infusion, mean ACTH levels rose significantly (P < 0.05) from a mean basal value of 3.14 ± 0.79 pmol/L to a peak of 10.39 ± 1.12 pmol/L at 45 min. During treatment with DP infusion and SAL injection, only a slight, but not significant, increase in ACTH levels was observed (peak value, 5.25 ± 1.22 pmol/L). When oCRH was injected during DP infusion, plasma ACTH values significantly (P < 0.05) increased from a mean basal value of 2.89 ± 0.96 pmol/L to a peak of 21.37 ± 3.43 pmol/L at 60 min. No significant changes in ACTH levels were observed when subjects were submitted to SAL injection during SAL infusion.



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  		Figure 1. Mean concentrations of plasma ACTH levels during the four treatments. Open arrows indicate the 60-min infusion of DP (4.3 ng/kg·min) or SAL. The filled arrow indicates the 2-min injection of oCRH (1 µg/kg BW) or SAL. Significant (P < 0.05) differences from basal at 0 min within each test are shown by an asterisk. {square}, SAL infusion plus SAL injection; {triangleup}, SAL infusion plus oCRH injection; {blacksquare}, DP infusion plus SAL injection; {circ}, DP infusion plus oCRH injection.

 
The differences in ACTH secretory response to the four different stimuli are represented by the ACTH AUC values in Fig. 2Go. The challenge by SAL infusion plus oCRH injection induced an increase in the ACTH AUC significantly higher than that observed after SAL infusion plus SAL injection (288.23 ± 61.90 vs. 5.78 ± 17.60 pmol/L·60 min; P < 0.05). Also, DP infusion plus oCRH injection resulted in an increase in the ACTH AUC significantly higher than that observed in DP infusion plus SAL injection (699.70 ± 91.80 vs. 47.92 ± 20.12 pmol/L·60 min; P < 0.05). No significant differences were found in the ACTH AUC between SAL infusion plus SAL injection and DP infusion plus SAL injection. The values of ACTH AUC observed during DP infusion plus oCRH injection were significantly higher than those observed during SAL infusion plus oCRH injection (699.70 ± 91.80 vs. 288.23 ± 61.90 pmol/L·60 min; P < 0.05).



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  		Figure 2. Mean integrated AUC for plasma ACTH responses to the four treatments. *, P < 0.05 vs. both SAL infusion plus SAL injection and DP infusion plus SAL injection; §, P < 0.05 vs. SAL infusion plus oCRH injection.

 
The basal and stimulated GAL levels are shown in Fig. 3Go. A high variability in GAL values was found between subjects. Basal GAL levels did not differ in the four experimental conditions. None of the stimuli caused a significant change in plasma GAL levels.



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  		Figure 3. Mean concentrations of plasma GAL during the four treatments. Open arrows indicate the 60-min infusion of DP (4.3 ng/kg·min) or SAL. The filled arrow indicates the 2-min injection of oCRH (1 µg/kg BW) or SAL. {square}, SAL infusion plus SAL injection; {triangleup}, SAL infusion plus oCRH injection; {blacksquare}, DP infusion plus SAL injection; {circ}, DP infusion plus oCRH injection.

 
No significant effect of any test on SBP, DBP, and HR values was found (data not shown), although one subject reported a slight increase in HR after DP infusion plus oCRH injection, and a mild increase in SBP and DBP was observed in two other subjects after the same stimulus.

Side-effects

Each subject experienced facial flush after CRH or DP administration. In one subject, this phenomenon was stronger when oCRH was injected during DP infusion.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
These results show that circulating GAL levels are not affected by stimulation of corticotrophs with either oCRH or the combined oCRH and DP treatments.

In experimental animals, progesterone seems to counterbalance the effect of estrogen on GAL levels in brain and plasma (11, 15). Therefore, women in the follicular phase of the menstrual cycle were studied when progesterone levels are low, and its effect is negligible, although the potential influence of sex steroids on GAL physiology in humans is not well understood.

It is well known that CRH represents the classical hypothalamic secretagogue for corticotrophs to release ACTH. In addition, AVP induces ACTH secretion (12) and potentiates ACTH release induced by oCRH when injected peripherally in humans (16). DP (dDAVP) is a synthetic analog of the neurohypophyseal AVP that has been shown to have lower pressor effects and to act predominantly through the renal V2 receptors (17). Although the effect of DP on ACTH secretion is well established in rats (18), the human data are still controversial. In fact, although DP has been shown to have negligible effects on circulating ACTH levels (19), more recent studies suggested that DP can potentiate CRH-induced ACTH release (13). Our results confirmed that DP, although ineffective on basal ACTH levels when administered alone (DP infusion plus SAL injection), is able to elicit the ACTH response to oCRH, as documented by the higher ACTH levels during DP infusion plus oCRH injection compared to those observed during SAL infusion plus oCRH injection. We also found that the oCRH-induced ACTH response was not associated with concomitant changes in GAL levels.

As GAL and ACTH (10) and their respective messenger ribonucleic acids (11) are located within corticotrophs of the human pituitary, one might expect a concomitant release of ACTH and GAL under certain stimuli. However, as our observations indicate, the secretory response of ACTH to CRH and DP stimuli was not accompanied by an elevation of GAL secretion from corticotrophs. Nevertheless, it is possible that the native vasopressin, and not DP, determines the release of GAL.

The lack of concomitant release of ACTH and GAL in response to oCRH and the combined oCRH and DP stimuli suggests that CRH and/or AVP are not the physiological secretagogues of pituitary GAL secretion, and that substances other than the above-mentioned hypothalamic peptides may be responsible for GAL secretion from corticotrophs. Our recent data (unpublished observations) have shown that no significant changes in circulating GAL levels occur after TRH, GnRH, and GHRH injections in man, further suggesting that GAL is probably not secreted from the pituitary gland in response to stimulations with hypothalamic releasing peptides. The major physiological role of pituitary GAL would seem, therefore, to be a paracrine or an autocrine effect. Earlier binding studies (20, 21), while detecting specific binding sites in the brain, have failed to demonstrate GAL receptors in the anterior pituitary. However, recent reports have shown the presence of GAL receptors in normal rat (22) and adenomatous human pituitary tissue (23).

The source of circulating GAL levels in man remains to be addressed. It has been shown that plasma GAL levels are lower in diabetic patients with autonomic dysfunction than in healthy subjects (24). These observations suggest that the peripheral and/or central nervous systems may play a role in regulating GAL levels in peripheral blood, although the site(s) at which the peptide is secreted remains unknown.

In conclusion, our results demonstrated that the elevation in ACTH plasma levels after treatment with either oCRH or the combination of oCRH and DP stimuli is not accompanied by a significant increase in circulating GAL levels. Further studies are needed to identify the role of GAL synthesized and stored in human corticotrophs and the factors that regulate its circulating levels in man.


   Acknowledgments
 
The authors thank Dr. Fabrizio Ablondi for his technical assistance.

Received July 23, 1996.

Revised October 14, 1996.

Accepted October 21, 1996.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Tatemoto K, Rokaeus A, Jornvall H, McDonald TJ, Mutt V. 1983 Galanin: a novel biologically active peptide from porcine intestine. FEBS Lett. 164:124–128.[CrossRef][Medline]
  2. Rokaeus A. 1987 Galanin a newly isolated biologically active neuropeptide. Trends Neurosci. 10:158–164.
  3. Merchenthaler I, Lopez FJ, Negro-Vilar A. 1993 Anatomy and physiology of central galanin-containing pathways. Prog Neurobiol. 40:711–769.[CrossRef][Medline]
  4. Merchenthaler I. 1991 The hypophysiotropic galanin system of the rat brain. Neuroscience. 44:643–654.[CrossRef][Medline]
  5. Lopez FJ, Meade EH, Negro-Vilar A. 1993 Endogenous galanin modulates the gonadotropin and prolactin proestrous surges in the rat. Endocrinology. 132:795–800.[Abstract]
  6. Ottlecz A, Samson WK, McCann SM. 1986 Galanin: evidence for a hypothalamic site of action to release growth hormone. Peptides. 7:51–53.[CrossRef][Medline]
  7. Bauer FE, Ginsberg L, Venetikou M, et al. 1986 Growth hormone release in man induced by galanin, a new hypothalamic peptide. Lancet. 2:192–196.[CrossRef][Medline]
  8. Giustina A, Licini M, Schettino M, et al. 1994 Physiological role of galanin in the regulation of anterior pituitary function in humans. Am J Physiol. 266:E57–E61.
  9. Steel JH, Gon G, O’Halloran DJ, et al. 1991 Galanin and vasoactive intestinal polypeptide are colocalized with classical pituitary hormones and show plasticity of expression. Histochemistry. 93:183–189.
  10. Vrontakis ME, Sano T, Kovacs K, et al. 1990 Presence of galanin-like immunoreactivity in nontumorous corticotrophs and corticotroph adenomas of the human pituitary. J Clin Endocrinol Metab. 70:747–751.[Abstract]
  11. Kaplan LM, Hooi SC, Abrczinkas DR, et al. 1992 Neuroendocrine regulation of galanin gene expression. Wenner Gren Symp. 58:43–65.
  12. Orth DN. 1992 Corticotropin-releasing hormone in humans. Endocr Rev. 13:164–191.[CrossRef][Medline]
  13. Newell-Price JDC, Edwards R, Perry LA, Besser GM, Grossman AB. Desmopressin causes ACTH and cortisol secretion in patients with Cushing disease but not in normal volunteers. Proc of the 77th Annual Meet of The Endocrine Soc. 1995; 99.
  14. Norusis MJ. 1985 SPSS-X advanced statistic guide. New York: McGraw-Hill.
  15. Kaplan LM, Gabiel SM, Koenig JI, et al. 1988 Galanin is an estrogen-inducible, secretory product of the rat anterior pituitary. Proc Natl Acad Sci USA. 85:7408–7412.[Abstract/Free Full Text]
  16. De Bold CR, Sheldon WR, De Cherney GS, et al. 1984 Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor. J Clin Invest. 73:533–538.
  17. Malerbi DA, Mendonça BB, Liberman B, et al. 1993 The desmopressin stimulation test in the differential diagnosis of Cushing’s syndrome. Clin Endocrinol (Oxf). 38:463–472.[Medline]
  18. Aizawa T, Yasuda N, Greer M, Sawyer W. 1982 In-vivo adrenocorticotropin-releasing activity of neurohypophyseal hormones and their analogs. Endocrinology. 110:98–104.[Abstract]
  19. Anderson KE, Arner B, Hedner P, Mulder JL. 1972 Effects of 8-lysine-vasopressin and synthetic analogues on release of ACTH. Acta Endocrinol (Copenh). 69:640–648.[Medline]
  20. Gaymann W, Falke N. 1990 Galanin lacks binding sites in the porcine pituitary and has no detectable effetc on oxytocin and vasopressin release from rat neurosecretory endings. Neurosci Lett. 112:114–119.[CrossRef][Medline]
  21. Hulting AL, Meister B, Carlsson L, Hilding A, Isaksson O. 1991 On the role of the peptide galanin in regulation of growth hormone secretion. Acta Endocrionol (Copenh). 125:518–525.[Medline]
  22. Wynick D, Smith DM, Ghatei M, Akinsanya K, et al. 1993 Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor. Proc Natl Acad Sci USA. 90:4231–4235.[Abstract/Free Full Text]
  23. Hulting AL, Land T, Berthold M, Langel U, Hokfelt T, Bartfai T. 1993 Galanin receptors from pituitary tumors assayed with human galanin as ligand. Brain Res. 625:173–176.[CrossRef][Medline]
  24. Sundkvist G, Bramnert M, Bergstrom B, Manhem P, Liljia B, Ahren B. 1992 Plasma neuropeptide Y (NPY. and galanin before and during exercise in type 1 diabetic patients with autonomic dysfunction. Diabetes Res Clin Pract. 15:219–226.[CrossRef][Medline]



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