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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2004-2184
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 7 4108-4111
Copyright © 2005 by The Endocrine Society

BRIEF REPORT

Median Eminence Dopaminergic Nerve Terminals: A Novel Target in Autoimmune Polyendocrine Syndrome?

Cristina Cocco, Antonella Meloni, Francesco Boi, Giovanni Pinna, Roberta Possenti, Stefano Mariotti and Gian-Luca Ferri

NEF-Laboratory, Department of Cytomorphology (C.C., G.-L.F.) and Endocrinology, Department of Medical Science (F.B., G.P., S.M.), University of Cagliari at Monserrato, 09042 Monserrato (Cagliari), Italy; Clinica Pediatrica II, Department of Biomedical Biotechnological Science (A.M.), University of Cagliari, 09100 Cagliari, Italy; and Department of Neuroscience (R.P.), Tor Vergata University, 00133 Rome, Italy

Address all correspondence and requests for reprints to: Prof. Gian-Luca Ferri, M.D., Department of Cytomorphology, Cittadella Universitaria, 09042 Monserrato (Cagliari), Italy. E-mail: ferri{at}unica.it.


   Abstract
Top
 Abstract
Introduction
 Patient and Methods
 Results
 Discussion
 References
 
Context: Autoantibodies to adenohypophyseal endocrine cells or to vasopressin neurohypophyseal neurons have long been known. Conversely, autoimmune targeting of further hypothalamic-hypophyseal structures, such as the blood-brain barrier-deprived median eminence, has been little studied.

Objective and Methods: We studied a case of autoimmune polyendocrine syndrome type I with GH secretory deficiency, a distinctly rare event in autoimmune polyendocrine syndrome type I. We used rat and bovine tissue substrates to study autoantibodies against hypothalamic-hypophyseal nerve structures and endocrine cells.

Results: In the study case, circulating autoantibodies selectively decorated median eminence dopaminergic nerve terminals, as well as pituitary gonadotropes, but not GHRH nerve terminals or pituitary somatotropes. Such autoantibodies appeared de novo in parallel with the onset of GH secretory deficiency, whereas no median eminence labeling was found in patients suffering of idiopathic GH deficiency (n = 7) or in healthy controls (n = 23).

Conclusions: The pathophysiological significance of our patient’s autoantibodies remains to be confirmed. Nonetheless, the heterogeneous neuroendocrine structures of the median eminence are pointed out as potential immune targets, relevant to autoimmune polyendocrinopathy, as well as to a wide range of other conditions.


   Introduction
Top
 Abstract
 Introduction
Patient and Methods
 Results
 Discussion
 References
 
IN THE HYPOTHALAMIC median eminence, release and interaction of many neurotransmitters and pituitary tropic factors is facilitated by the absence of a blood-brain barrier. Such anatomical feature, however, opens the way for circulating antibodies to reach and potentially affect neuroendocrine areas regulating the pituitary, hence a cascade of further endocrine glands, organs, and tissues. Surprisingly, autoimmune targeting of median eminence nerve structures has been little investigated, although autoantibodies to vasopressin/oxytocin neurohypophyseal neurons or to adenohypophyseal endocrine cells have long been discovered (1, 2, 3).

Autoimmune polyendocrine syndrome type I (APS I) is a rare autosomal recessive disorder caused by mutations in the AIRE gene (4, 5, 6, 7) and may show a wide range of autoimmune changes (6, 7, 8). In association with certain clinical features, various autoantibodies to neurotransmitter- or hormone-synthesizing enzymes, such as tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), glutamic acid decarboxylase, and tryptophan hydroxylase were demonstrated (7, 9, 10). Conversely, anterior hypopituitarism is very rare (11, 12, 13) and has been ascribed to autoimmune hypophysitis, although pituitary autoantibodies were so far demonstrated in only one patient (13).

We studied a case of APS I in which an unusual arrest of growth prompted us to investigate GH secretion and to search for autoantibodies targeting pituitary endocrine cells and their upstream neuroendocrine regulatory pathway in the hypothalamus-pituitary region.


   Patient and Methods
Top
 Abstract
 Introduction
 Patient and Methods
Results
 Discussion
 References
 
Case report and clinical course

A girl, the second of two children born to healthy, nonconsanguineous Sardinian parents, was diagnosed with APS I at 4.5 yr, when she presented with hypoparathyroidism and mucocutaneous candidiasis. To characterize the patient’s molecular defects, the 14 exons of the AIRE gene, including the intron-exon junctions, were sequenced using primers and conditions described previously (14, 15). Sequence analysis showed a compound heterozygosity for the c.415 C>T (p.R139X) and c.967_979del (p.C322fsX372) mutations. Addison’s disease became apparent at 6 yr, whereas at 10 yr, a marked, progressive growth deceleration became apparent (Fig. 1AGo). At 12 yr, height was 128 cm (–3 SD), weight 28 kg (–1.2 SD), bone age 8.8 yr, and the patient was still prepuberal (Tanner stages P1 and B1). Nonendocrine causes of growth failure were excluded, and magnetic resonance imaging showed a small pituitary gland. Serum T3, T4, and prolactin were normal. FSH, LH, estradiol, and IGF-I were low (1.7 and 0.3 mU/ml and <15 and 94 ng/ml vs. normal range at patient’s age, 3.0–12 and 1.0–18.5 mU/ml and >30 and 108–648 ng/ml, respectively). Nocturnal pulsatile GH secretion was markedly reduced (mean serum GH, 0.8 ng/ml; normal at subject’s age, >3 ng/ml). GH secretion after insulin-induced hypoglycemia or GHRH was normal, whereas neither clonidine nor L-dopa induced a normal GH raise (Fig. 1BGo; normal peak GH, >10 ng/ml at patient’s age). LHRH (100 µg iv) induced a prepuberal response of serum LH and FSH (peak LH, 2.1 mIU/ml; peak FSH, 14 mIU/ml). Autoantibodies to adrenocortical, gonadal, and gastric parietal cells and liver-kidney microsomes were detected by indirect immunofluorescence, whereas antiendomysium, -islet cells, -nucleus, -mitochondria, -smooth muscle, -thyroglobulin, and -thyroid peroxidase were negative (kits from Bio-Rad Laboratories, Perth, UK; Immulite, Medical Systems, Genoa, Italy). Defective release of GHRH was hypothesized, possibly involving alteration of catecholaminergic pathways. Human recombinant GH was started (0.18 mg/kg·wk) and resulted in increased growth (5.3 cm over the latest 12 months) and serum IGF-I (428 ng/ml). The patient is presently 13.8 yr old and is still prepuberal.



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  		FIG. 1. A, A severe reduction in growth rate is shown, starting around 10 yr. B, Serum GH showed a subnormal response to either clonidine or L-dopa, whereas it increased normally after insulin or GHRH (normal response > 10 ng/ml, all curves).

 
Autoantibodies to hypothalamus-pituitary components

Three samples of the patient’s serum were studied, taken while growth was normal (7 yr, prearrest serum) and after growth deceleration (11 and 13 yr, postarrest sera). Sera were obtained from cases of isolated, idiopathic GH deficiency (n = 7; age, 4–13 yr) and healthy controls (n = 23; age, 7–60 yr). Bovine tissues (from local abattoir, n = 6 of each sex), either snap-frozen (unfixed), paraformaldehyde-, or periodate-lysine paraformaldehyde-fixed, and paraformaldehyde perfusion-fixed rat hypothalami (Sprague Dawley, n = 3) were used. Upon snap-freezing in cryoembedding medium (16), sections (5–15 µm) were obtained with a cold-knife Microm HM-560 cryomicrotome. For immunohistochemistry, sera were diluted in PBS [10 mmol/liter PO4 (pH 7.2–7.4), 150 mmol/liter NaCl] containing 30 ml/liter normal serum of the second antibody donor species (donkey), and normal bovine/rat serum (when using bovine or rat tissue, respectively; 30 ml/liter). Target characterization was carried out with antibodies to anterior and posterior pituitary hormones (P. Berger, National Institute of Diabetes and Digestive and Kidney Diseases; Chemicon, Temecula, CA); tropic factors: CRH, GHRH, GnRH, and somatostatin (Chemicon; Affiniti-Biomol, Exeter, UK); neuropeptides: neuropeptide Y, vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and galanin (J. M. Polak and A. Arimura, Affiniti-Biomol); catecholamine-synthesizing and other enzymes (TH, dopamine ß-hydroxylase, phenylethanolamine methyltransferase, and neuron-specific enolase, Affiniti-Biomol). Species-specific secondary antibodies used (Jackson Immunoresearch, West Grove, PA; Alexa 488-conjugate, Molecular Probes, Leiden, The Netherlands) were conjugated with fluorochromes emitting in green (Cy 2, Alexa 488), yellow-red (Cy 3), or blue (aminomethylcoumarin). Routine controls included substitution of each antibody, in turn, with PBS.

Samples of bovine pituitary and medial hypothalamus (n = 4) were extracted at 4 C in PO4 buffer containing 1% (vol/vol) protease inhibitor cocktail (Sigma, Milan, Italy). Tissues were extracted three times using a polytron PT3100 homogenizer (Kinematica, Lucerne, Switzerland), centrifuged, and supernatants were pooled and precipitated at –20 C overnight with 6 volumes of ethanol-methanol-acetone mixture (2:1:1, vol/vol). Pellets were dissolved and run on NuPAGE 10% polyacrylamide gel in 3-[N-morpholino]propanesulfonic acid buffer, and blotted onto nitrocellulose for Western-blot analysis. Western blots were incubated overnight at 4 C with the patient’s sera diluted 1:200 and 1:800 and detected with the ECL system (Pierce, Rockford, IL).


   Results
Top
 Abstract
 Introduction
 Patient and Methods
 Results
Discussion
 References
 
The patient’s postarrest sera showed labeling at high titer (>1:400) in a thin layer of nerve terminals on the outermost surface of the median eminence and in hypothalamic perikarya in the lower lateral wall of the third ventricle (Fig. 2Go, A and C). The posterior pituitary was negative, whereas autoantibody-reactive endocrine cells (>1:400 titer) were numerous in the adenohypophyseal pars distalis (Fig. 2Go, G and I) and scattered in the pars tuberalis (Fig. 2AGo). The prearrest serum (taken at 7 yr, while growth was still normal) only produced weak, diffuse pituitary staining (≤1:30) with no neuronal labeling. Proper preservation of the latter serum was confirmed using adrenal sections, in which intense labeling was obtained. Neuronal labeling was widely although incompletely colocalized with the catecholaminergic enzymes TH (Fig. 2Go, B and F) and AADC, but not with either anti-GHRH (Fig. 2DGo) or with any of the other antibodies tested, whereas neuron-specific enolase showed a far wider localization. Hence, labeling appeared to be selective for dopaminergic tuberoinfundibular and tuberohypophysial pathways (except posterior pituitary projections). Reactive endocrine cells were largely identified as gonadotropes and thyreotropes (>95 and approximately 5%, respectively, Fig. 2JGo), and mostly also labeled for AADC (Fig. 2HGo). None of GH deficiency or healthy control sera (tested at 1:8 dilution) labeled hypothalamic perikarya or median eminence nerve terminals. As expected, at the same dilution several sera (four of seven GH deficiency, eight of 23 healthy controls) resulted in pituitary endocrine cell labeling.



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  		FIG. 2. Labeling by the patient’s postarrest serum in the hypothalamus-pituitary complex. Immunoreactive nerve terminals formed a dense layer in the outermost superficial median eminence (A and C, patient’s serum; bovine, scale bar = 50 µm) and were also labeled for TH (B vs. A, double labeling) but not for GHRH (D vs. C). Similarly, the patient’s autoantibodies showed a wide, although incomplete, colocalization with TH in perikarya of the medial hypothalamus (E, patient’s serum vs. F, TH; arrows, noncolabeled features; rat tissue, scale bar = 100 µm). Many endocrine cells were decorated by the patient’s serum in pars distalis (G and I, bovine, scale bar = 60 µm) and pars tuberalis (A), mostly colabeled for aromatic AADC (H vs. patient’s serum, G) and identified as gonadotropes and a few thyreotropes (triple labeling; J, solid arrows; green labeling for LH; empty arrows, blue labeling for TSH; vs. I, patient’s serum).

 
In Western-blot experiments (cytosolic extracts of bovine hypophysis), the patient’s postarrest serum revealed bands in the 45,000–52,000 molecular weight range and at approximately 95,000 molecular weight. The prearrest patient’s serum was negative, whereas seven of 18 healthy controls and four of seven idiopathic GH deficiency cases tested resulted in at least some labeling of comparable bands at either dilution tested (1:200 and 1:800). Hence, we failed to identify specific autoantibody-related molecular bands in our test case.


   Discussion
Top
 Abstract
 Introduction
 Patient and Methods
 Results
 Discussion
References
 
A major, novel finding in our patient is the appearance of high-titer (>1:400) autoantibodies to median eminence dopaminergic nerve structures but not to GH cells or GHRH neurons or terminals at a time when she developed a sudden, rapidly progressive arrest of growth. Such finding was highly selective, with none of our idiopathic GH deficiency or healthy control sera producing hypothalamic labeling. Pending identification of the relevant target/s and validation against human antigens, one may speculate that our patient’s autoantibodies might have interacted with median eminence dopaminergic terminals to alter GHRH release, in keeping with the conserved GH response to GHRH and its subnormal raise after L-dopa. Although the role of dopamine in GH regulation remains unclear, synapses between catecholaminergic axons and GHRH neurons may mediate stimulation of GH release via GHRH (17).

Alternatively, autoantibodies might be secondary to hypothalamic changes that induced GH deficiency. Interestingly, low-titer antipituitary autoantibodies have been found in a proportion of patients with endocrine autoimmune diseases and of normal individuals (2, 18), in keeping with the labeling we found with GH deficiency and control sera at low dilution. Conversely, higher titer (>1:8) pituitary autoantibodies were associated with GH deficiency (18), and characterization of the relevant pituitary target cell/s could add to their value as markers of autoimmune hypophyseal involvement. In our young patient, long-term follow-up may help clarify the relevance of her autoantibodies targeting pituitary gonadotropes and associated with low gonadotropin levels and a persistent prepuberal state.

As mentioned, GH deficiency is very rare in APS I patients (6, 7, 8, 11, 12, 13) and was ascribed to autoimmune hypophysitis, at least in one case in association with (uncharacterized) pituitary autoantibodies (13). Conversely, aromatic AADC, tryptophan hydroxylase, and TH autoantibodies are comparatively common in APS I patients, in association with autoimmune hepatitis and vitiligo, intestinal dysfunction, and alopecia, respectively (9, 10). TH and AADC, however, are also present in many catecholaminergic neurons; hence, it is somewhat surprising that such autoantibodies were not so far linked to possible targeting of nervous or neuroendocrine tissue. Nonetheless, TH and AADC autoantibodies could at least partly explain the labeling of dopaminergic neurons and terminals we found. We were unable to carry out preabsorbtion tests of our immunostaining with the relevant TH and AADC proteins. However, coincidence of our patient’s autoantibody labeling with TH- and AADC-immunoreactive neurons and endocrine cells was far from complete, suggesting that a further target molecule is likely to be involved.

A 49-kDa pituitary cytosolic protein from the human pituitary has been recognized as a major autoantibody target in hypophysitis (3) and was identified as {alpha}-enolase (19). Using bovine pituitary extracts, we could not identify molecular band(s) matching the specific labeling observed in immunocytochemistry. The complexity of such issue is underlined by the previous finding of nonspecific autoantibody-reactive protein bands, even in human pituitary extracts, in the 88,000–95,000 molecular weight range (2, 3).

In conclusion, high-titer autoantibodies to median eminence dopaminergic structures appeared in our patient at a time when she developed a sudden, rapidly progressive arrest of growth. Whether autoantibodies may have induced such change or represent an epiphenomenon remains to be determined. Recently, sera from a few patients affected by anorexia nervosa/bulimia were found to label median eminence LHRH terminals, largely due to anti-LHRH autoantibodies (20). Our findings go further to show that specific structures within the hypothalamic median eminence can be the target of autoimmune activation parallel to clinical changes. The relevant implications may encompass many areas of endocrine and neuroendocrine disease, as well as so-called functional neuro/endocrine conditions.


   Acknowledgments
 
Informed consent for the study was obtained from the patient’s parents. We thank G. Boi, F. Incollu, and the COALBE Company for bovine tissue samples; National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, U.S. Department of Agriculture, P. Berger, A. Arimura, and J. M. Polak for antibodies; and C. Rosatelli for expert advice.


   Footnotes
 
G.-L.F. designed tissue studies, C.C. carried out immunocytochemical experiments with cooperation from F.B., A.M. was in charge of the patient and clinical studies, R.P. ran Western blots with cooperation from G.P., S.M. initiated and coordinated the study, and G.-L.F. and C.C. wrote the paper.

This work was supported by Research Grants from the Italian Ministry of University and Research (COFIN Grants 2002067915_002 and 2002067915_001) and from the University of Cagliari.

CONFLICT OF INTEREST STATEMENT: None of the funding bodies had any part in the design, conduction, writing, or submission of the study. No conflicts of interest affect any of the authors with respect to the present report and its contained data. All authors had full access to all data in the study and take final responsibility for the decision to submit for publication in the form submitted.

First Published Online April 26, 2005

Abbreviations: AADC, L-Amino acid decarboxylase; APS I, autoimmune polyendocrine syndrome type I; TH, tyrosine hydroxylase.

Received November 5, 2004.

Accepted April 15, 2005.


   References
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 Abstract
 Introduction
 Patient and Methods
 Results
 Discussion
 References
 

  1. Scherbaum WA, Bottazzo GF 1983 Autoantibodies to vasopressin cells in idiopathic diabetes insipidus: evidence for an autoimmune variant. Lancet 1:897–901[Medline]
  2. Bellastella A, Bizzarro A, Coronella C, Bellastella G, Sinisi AA, De Bellis A 2003 Lymphocytic hypophysitis: a rare or underestimated disease? Eur J Endocrinol 149:363–376[Abstract]
  3. Crock PA 1998 Cytosolic autoantigens in lymphocytic hypophysitis. J Clin Endocrinol Metab 83:609–618[Abstract/Free Full Text]
  4. Aaltonen J, Björses P, Perheentupa J, Horelli-Kuitunen N, Palotie A, Peltonen L, Lee YS, Francis F, Henning S, Thiel C, Leharach H, Yaspo M-L 1997 An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet 17:399–403[CrossRef][Medline]
  5. Ahonen P, Myllarniemi S, Sipila I, Perheentupa J 1990 Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 322:1829–1836[Abstract]
  6. Betterle C, Greggio NA, Volpato M 1998 Clinical review 93: autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 83:1049–1055[Free Full Text]
  7. Perheentupa J 2002 APS-I/APECED: the clinical disease and therapy. Endocrinol Metab Clin North Am 31:295–320[CrossRef][Medline]
  8. Dittmar M, Kahaly GJ 2003 Polyglandular autoimmune syndromes: immunogenetics and long-term follow-up. J Clin Endocrinol Metab 88:2983–2992[Abstract/Free Full Text]
  9. Perniola R, Falorni A, Clemente MG, Forini F, Accogli E, Lobreglio G 2000 Organ-specific and non-organ-specific autoantibodies in children and young adults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Eur J Endocrinol 143:497–503[Abstract]
  10. Soderbergh A, Myhre AG, Ekwall O, Gebre-Medhin G, Hedstrand H, Landgren E, Miettinen A, Eskelin P, Halonen M, Tuomi T, Gustafsson J, Husebye ES, Perheentupa J, Gylling M, Manns MP, Rorsman F, Kampe O, Nilsson T 2004 Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 89:557–562[Abstract/Free Full Text]
  11. Arvanitakis C, Knouss RF 1973 Selective hypopituitarism. Impaired cell-mediated immunity and chronic mucocutaneous candidiasis. JAMA 225:1492–1495[Abstract/Free Full Text]
  12. Franzese A, Valerio G, Di Maio S, Iannucci MP, Bloise A, Tenore A 1999 Growth hormone insufficiency in a girl with the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Endocrinol Invest 22:66–69
  13. Ward L, Paquette J, Seidman E, Huot C, Alvarez F, Crock P, Delvin E, Kampe O, Deal C 1999 Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. J Clin Endocrinol Metab 84:844–852[Abstract/Free Full Text]
  14. Rosatelli MC, Meloni A, Meloni A, Devoto M, Cao A, Scott HS, Peterson P, Heino M, Krohn KJ, Nagamine K, Kudoh J, Shimizu N, Antonarakis SE 1998 A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. Hum Genet 103:428–434[CrossRef][Medline]
  15. Scott HS, Heino M, Peterson P, Mittaz L, Lalioti MD, Betterle C, Cohen A, Seri M, Lerone M, Romeo G, Collin P, Salo M, Metcalfe R, Weetman A, Papasavvas MP, Rossier C, Nagamine K, Kudoh J, Shimizu N, Krohn KJ, Antonarakis SE 1998 Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins. Mol Endocrinol 12:1112–1119[Abstract/Free Full Text]
  16. Cocco C, Melis GV, Ferri GL 2003 Embedding media for cryomicrotomy: an applicative reappraisal. Appl Immunohistochem Mol Morphol 11:274–280[Medline]
  17. Muller EE, Locatelli V, Cocchi D 1999 Neuroendocrine control of growth hormone secretion. Physiol Rev 79:511–607[Abstract/Free Full Text]
  18. De Bellis A, Bizzarro A, Conte M, Perrino S, Coronella C, Solimeno S, Sinisi AM, Stile LA, Pisano G, Bellastella A 2003 Antipituitary antibodies in adults with apparently idiopathic growth hormone deficiency and in adults with autoimmune endocrine diseases. J Clin Endocrinol Metab 88:650–654[Abstract/Free Full Text]
  19. O’Dwyer DT, Smith AI, Matthew ML, Andronicos NM, Ranson M, Robinson PJ, Crock PA 2002 Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as {alpha}-enolase. J Clin Endocrinol Metab 87:752–757[Abstract/Free Full Text]
  20. Fetissov SO, Hallman J, Oreland L, Af Klinteberg B, Grenback E, Hulting AL, Hokfelt T 2002 Autoantibodies against {alpha}-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients. Proc Natl Acad Sci USA 99:17155–17160[Abstract/Free Full Text]



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