Biomedical subjects

F Aragona

Publications and source records attributed to F Aragona.

At least 19 recordsLinked to original sources

PubMed2006

Difference in Ki67 and thymidylate synthase expression in primary tumour compared with metastatic nodes in breast cancer patients.

Breast cancer is a heterogeneous disease, so therapeutic predictive biological markers need to be identified. To date an accurate evaluation of predictive markers is mainly done at the primary site; however, the main goal of adjuvant therapy for breast cancer is the control of micrometastases. The aim of this study is to assess as therapeutic and/or prognostic marker, the proliferation status of primary tumors and involved nodes as measured by Ki67 and thymidylate synthase (TS) expression, in 30 breast cancer node positive patients. TS is the main target of 5-fluorouracil (5-FU) activity, and its overexpression is one of the mechanisms of 5-FU drug resistance; however, in some studies its absence is responsible for a worse response to 5-FU. Our results show that malignant cells of involved nodes were in a post mitotic phase of the cell cycle, and show a low proliferation index and TS expression, while the primary tumours and controls, were strongly positive. On these basis we can hypothesize that these cells could be less sensitive to 5-FU. Further studies are necessary to identify other mechanisms responsible for their metastasing capability and/or for their aggressiveness.

Antigens, Neoplasm↗

PubMed2005

Incidence of prostate cancer in Sicily: results of a multicenter case-findings protocol.

OBJECTIVE: To establish the incidence of prostate cancer (PCa) in Sicily in patients who entered an early detection protocol. METHODS: From February 2002 to February 2004, 16,298 subjects aged 40-75 entered the protocol. Patients with suspicious DRE, PSA>10 ng/ml, PSA<or=2.5 ng/ml, from 2.6 to 4 ng/ml or from 4.1 to 10 ng/ml with F/T PSA of <or=15%, <or=20% and <or=25% respectively underwent needle biopsy according to an extensive protocol. RESULTS: 3266 patients were eligible for biopsy; PSA was <or=4 in 12.7% and <or=10 ng/ml in 63.9% of patients. A PCa was found in 1171 cases (36.9%) with a relationship between PCa incidence and PSA and age respectively (chi2-test, p<0.0001); 51.8% of patients with PCa had a PSA<10 and 8.8% a PSA<4 ng/ml; 49% were clinically staged as T1c. The estimated odds ratios for each age group showed increased risk for PCa in the fourth decade with PSA between 2.6 and 4 ng/ml (12.5 times higher) and in the fifth decade with PSA between 4.1 and 10 ng/ml (6.2 times higher). CONCLUSIONS: Age and serum PSA levels are the major risk factors for PCa. On their basis it is possible to modulate the most suitable timing for early diagnosis in individual patients.

Adult↗

PubMed2005

Prediction by quantitative histology of pathological stage in prostate cancer.

AIMS: To find a predictor of extraprostatic extension in clinically localized prostate cancer (PCa), pre-operative ultrasound-guided prostate needle biopsies and clinico-pathological data were reviewed. METHODS: One hundred and eighty-three consecutive patients who underwent radical retropubic prostatectomy for clinical T1-T2 PCa and serum PSA <10 ng/ml were reviewed. Pre-operative biopsy was performed according to an extended protocol and whole-mount prostatectomy specimens were processed. The following biopsy variables were categorized to this analysis: Gleason score (< or =6, >6), TPC (< or =20%; >20%), GPC (< or =50%; >50%), cancer-positive cores (< or =2; >2), cancer-positive cores in both lateral portions (yes; no), PCa (monolateral; bilateral). RESULTS: Only 60/183 specimens showed an organ-confined PCa; the remaining ones showed pT3a in 57 cases, pT3b in 11 and pT3 with positive surgical margins in 55. A locally advanced PCa was found in 60.2 and 76.8% of T1c and T2 clinical stage, respectively. The positive predictive value and negative predictive value of biopsy findings to predict a locally advanced PCa was 89.9 and 75%, respectively. All biopsy variables associations were statistically significant; however, among these variables (non-categorized), in multivariate logistic regression analysis, only GPC was significantly associated with pathologic stage (odds ratio estimate was 1.075, 95% CI: 1.053-1.098). CONCLUSIONS: Quantitative histology, especially GPC, seems to be helpful for pre-operative staging of PCa in patients with T1c-T2 clinical stage and PSA < 10 ng/ml.

Aged↗

PubMed2005

Isolated local recurrence of renal neoplasm with caval involvement 16 years after radical nephrectomy.

OBJECTIVE: To report a case of local recurrence 16 years after radical nephrectomy; to analyse literature data concerning, treatment and prognosis. METHODS/RESULTS: We report a case of local recurence associated with caval trombosis who was underwent an en-bloc resection of vena cava along with pericaval lesion and caval replacement with PTFE prosthesis. The Authors reviewed and analysed literature data. CONCLUSIONS: Local recurrence after radical nephrectomy is rare as it is reported only in 2-4% of patients. This condition is even rarer beyond 10 years especially if associated with caval trombosis. A case of isolated local recurrence of renal cell carcinoma with caval involvement 16 years after radical nephrectomy is described herein. To the best of our knowledge, this is the first case reported in literature. This case highlights the opportunity of a periodic checkup of patients submitted to radical nephrectomy, even many years after surgery.

Aged↗

PubMed2004

Clinical relevance of thymidylate synthase expression in the signet ring cell histotype component of colorectal carcinoma.

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas.

Adult↗

PubMed2004

Cholecystokinin (CCK) stimulates aldosterone secretion from human adrenocortical cells via CCK2 receptors coupled to the adenylate cyclase/protein kinase A signaling cascade.

Cholecystokinin (CCK) IS a regulatory peptide that acts via two receptor subtypes, CCK1-R and CCK2-R. RT-PCR demonstrated the expression of both CCK1-R and CCK2-R in the zona glomerulosa (ZG), but not zona fasciculata-reticularis cells of the human adrenal cortex. CCK and the CCK2-R agonist pentagastrin enhanced basal aldosterone secretion from ZG cells without affecting cortisol production from zona fasciculata-reticularis cells. The aldosterone response to CCK and pentagastrin was suppressed by a CCK2-R antagonist, but not by a CCK1-R antagonist. Pentagastrin evoked a sizeable cAMP, but not inositol triphosphate, response from ZG cells, whereas CCK plus CCK2-R antagonist was ineffective. The cAMP response to pentagastrin was abrogated by CCK2-R antagonist or the adenylate cyclase inhibitor SQ-22536, and the aldosterone response was abolished by both SQ-22536 and the protein kinase A inhibitor H-89. Both CCK and pentagastrin increased steroidogenic acute regulatory protein mRNA expression in ZG cells; the effect was abrogated by CCK2-R antagonist. We conclude that CCK exerts secretagogue action on human ZG cells, acting through CCK2-Rs coupled to the adenylate cyclase/protein kinase A signaling cascade, which, in turn, stimulates the expression of steroidogenic acute regulatory protein, the rate-limiting step of steroidogenesis.

Adenylyl Cyclases↗

PubMed2003

Does the adjunct of ecographic contrast medium Levovist improve the detection rate of prostate cancer?

OBJECTIVES: To evaluate whether the adjunct of an ultrasound contrast medium improves the detection rate of prostate cancer. METHOD: In 34 patients, scheduled to undergo a trans-perineal extended prostate biopsy, we carried out a color-Doppler ultrasound (CDU) of the prostate before and after i.v. injection of Levovist, an ultrasound contrast medium. Further bioptic samples were taken in the areas where a marked increase in vascularization was noticed. RESULTS: The overall diagnostic sensitivity, specificity and efficiency were respectively 72.7, 56.2 and 62.9% for transrectal ultrasound (TRUS); 80, 56.2 and 65.3% for CDU and 88.8, 54.5 and 68% for CDU after Levovist injection; 66.5, 72.6 and 65.1% for digito-rectal examination (DRE); 100, 51.4 and 65.4% for total PSA; and 100, 88.8 and 94.3% for PSA free/total. In the 16 patients with prostate carcinoma, the sensitivity of CDU after Levovist was 92.3, 66% for both DRE and TRUS, and 80% for DRE plus TRUS. CONCLUSIONS: Considering the cost and the results obtained (high sensitivity and low specificity), a routine use of Levovist does not seem indicated in patients undergoing prostatic biopsy. An exception may be represented by patients with both negative DRE and TRUS.

Aged↗

PubMed2003

Biological aggressiveness evaluation in prostate carcinomas:immunohistochemical analysis of PCNA and p53 in a series of Gleason 6 (3+3) adenocarcinomas.

We selected 63 prostate tumors with Gleason's grade 6 (3+3), commonly showing both tubular and cribrous patterns. We compared in both patterns the expression of two of the most used biologic markers: PCNA and p53, with the aim to verify the validity of the Gleason's grading system to compare the morphologic grade with biologic aggressiveness and prognostic value. We did not find any statistical difference in the protein immunopositivity, indicating that both patterns could have identical biologic behaviour; then we confirmed the validity of Gleason's system for considering both tubular and cribrous patterns as an intermediate grade of tumoral differentiation. Moreover, we found a linear relationship between the increase of PCNA and the accumulation of mutated p53; this datum could confirm the hypothesis that p53 mutation is a late event in prostate carcinogenesis.

Adenocarcinoma↗

PubMed2002

Endothelin-1[1-31]: a novel autocrine-paracrine regulator of human adrenal cortex secretion and growth.

Endothelin (ET)-1[1-21] stimulates steroid secretion and zona glomerulosa growth and is expressed in the human and rat adrenal cortex together with its receptor subtypes A and B (ETA and ETB). Although ET-1[1-21] is generated from bigET-1 by an ET-converting enzyme (ECE-1), there is evidence of an alternative chymase-mediated biosynthetic pathway leading to the production of an ET-1[1-31] peptide, the role of which in adrenal pathophysiology is largely unknown. Gene expression and immunohistochemical studies allowed localization of chymase in the normal human adrenal cortex. Sizable amounts, not only of ET-1[1-21] but also of ET-1[1-31], were found in the adrenal vein plasma of three patients. ET-1[1-21] and ET-1[1-31] elicited a clear-cut secretory response by dispersed human adrenocortical cells, ET-1[1-31] being significantly less potent than ET-1[1-21]. The secretagogue effect of ET-1[1-31] was abolished by the ETA receptor antagonist BQ-123 and was unaffected by the ETB receptor antagonist BQ-788. Because, in humans, the secretagogue effect of ET-1[1-21] involves both ETA and ETB receptors, the weaker action of ET-1[1-31] could be attributable to a selective ETA receptor activation. Two lines of evidence support this contention: 1) ET-1[1-31] was more effective than ET-1[1-21] in stimulating ETA-mediated cell proliferation of human adrenocortical cells cultured in vitro; and 2) autoradiography showed that a) ET-1[1-31] displaced in vitro [(125)I]ET-1[1-21] binding to the ETA, but not ETB receptors, in human internal thoracic artery rings; and b) BQ-123, but not BQ-788, eliminated [(125)I]ET-1[1-31] binding in the rat adrenal cortex.

Adrenal Cortex↗

PubMed2001

Human pheochromocytomas, but not adrenal medulla, express glucagon-receptor gene and possess an in vitro secretory response to glucagon.

Glucagon-receptor mRNA was detected by reverse transcription-polymerase chain reaction in three human pheochromocytomas, but not in four normal adrenal medullas. Quantitative autoradiography demonstrated the presence of abundant [(125)I-Thyr(10)]glucagon binding sites in pheochromocytomas, which were displaced by both cold glucagon and the glucagon receptor antagonist Des-His(1)[Glu(9)]glucagon amide (GR-A). Adrenal medulla was weakly labeled, and the binding was not displaced by GR-A. Glucagon enhanced epinephrine and norepinephrine release by pheochromocytoma slices, minimal and maximal effective concentrations being 10(-8) M and 10(-6) M. Adrenomedullary slices evidenced a weak catecholamine response only to 10(-5) M glucagon. GR-A abolished the secretory response to glucagon of pheochromocytomas, but not of adrenal medullas. Collectively, these findings indicate that human pheochromocytomas, but not adrenal medulla, express glucagon receptors and possess a marked secretory response to glucagon, thereby providing the rationale to explain the specificity of the glucagon provocative test in the diagnosis of pheochromocytoma.

Adrenal Gland Neoplasms↗

PubMed2001

PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells.

Parathyroid hormone (PTH) and PTH-related peptide (PTH-RP) are two hypercalcemic hormones that share a common receptor subtype, the PTH/PTH-RP receptor. PTH and PTH-RP concentration dependently enhanced basal aldosterone and cortisol secretion from dispersed human adrenocortical cells, with a maximal effective concentration (approximately 2-fold increase) of 10(-8) M. The secretagogue effect of 10(-8) M PTH or PTH-RP was abolished by the PTH/PTH-RP receptor antagonist [Leu11,D-Trp12]-PTH-RP-(7-34)-amide (10(-6) M). PTH and PTH-RP (10(-8) M) raised cAMP and inositol-triphosphate release by dispersed adrenocortical cells, and these effects were blocked by the adenylate cyclase inhibitor SQ-22536 (10(-4) M) and the phospholipase C (PLC) inhibitor U-73122 (10(-5) M), respectively. SQ-22536 (10(-4) M) and U-73122 (10(-5) M) partially inhibited aldosterone and cortisol response to 10(-8) M PTH and PTH-RP; when added together, they abolished it. Similar results were obtained by using the protein kinase (PK)A and PKC inhibitors H-89 and calphostin C (10(-5) M). It is concluded that PTH and PTH-RP exert a sizeable secretagogue action on the human adrenal cortex, probably acting through the PTH/PTH-RP receptor coupled with both adenylate cyclase/PKA- and PLC/PKC-dependent signaling cascades.

Adenine↗

PubMed2001

Resolution of Ménétrier's disease after Helicobacter pylori eradicating therapy.

Some cases of Ménétrier's disease associated with Helicobacter pylori (HP) have recently been reported in the literature. We report here the case of a 51-year-old man with a diagnosis of Ménétrier's disease who had previously been unsuccessfully treated with H(2) antagonists. A subsequent demonstration of HP infection led us to treat the patient with an eradicating therapy which prompted complete regression of clinical symptoms, resolution of the gastric endoscopic picture, and absence of HP on gastric histology. This result, in accordance with others in the literature, indicates an eventual association of HP infection with Ménétrier's disease and that consequent therapy is mandatory.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Percutaneous liver biopsy: a safe outpatient procedure?

Following the discovery of hepatitis C virus, more liver biopsies (LB) than before are being performed to assess the severity of liver disease. In this study, following the recommendations for outpatient LB made by the Patient Care Committee of the American Gastroenterological Association, we assessed the feasibility and benefits of LB performed as an outpatient versus inpatient procedure over the last 7 years in our centre. The study included 1,581 patients consecutively examined in our institute; all LBs were performed by a single operator with a 16-gauge needle using the Menghini technique, and in all cases the puncture site was determined using prebiopsy ultrasound. Liver lesions were classified using grading and staging scores. Ultrasound-guided LB of focal lesions were excluded from this study. LB was performed on 1,318 outpatients and 263 hospitalized patients. The mean age of the hospitalized patients was higher than that of the outpatients (p < 0.0001). As major side effects, one death and one haemoperitoneum requiring blood transfusion were recorded in the hospitalized patients. As minor side effects, one haemorrhage occurred in the hospitalized patients, whereas a case of haemobilia and 2 cases of subcapsular haematoma were recorded in the outpatients. In both groups pain at the puncture site was the most frequent minor complication which easily resolved after non-steroid drug administration. Severe histological diagnoses, both in terms of grading and staging, were significantly associated with hospitalized patients. In conclusion, by carefully selecting patients and using prebiopsy ultrasound to assess the puncture site, outpatient LB can be safely performed in most cases; this procedure should be more widely used, because it has met with the favour of patients who are able to return home the same day and reduces public health care service costs.

Adult↗

PubMed2001

Human pheochromocytomas express orexin receptor type 2 gene and display an in vitro secretory response to orexins A and B.

Orexins A and B are hypothalamic peptides, that act through two receptor subtypes, called OX1-R and OX2-R. OX1-R selectively binds orexin A, whereas OX2-R is nonselective for both orexins. High levels of OX1-R mRNA and low levels of OX2-R mRNA have been previously detected in the human adrenal cortex and medulla. Here we demonstrated by RT-PCR the expression of the OX2-R, but not the OX1-R, gene in 10 benign secreting pheochromocytomas. Both orexins A and B stimulated catecholamine secretion from pheochromocytoma slices; the maximal effective concentration was 10(-8) mol/liter. Orexins A and B (10(-8) mol/liter) increased IP3, but not cAMP production, by tumor slices, and the effect was blocked by the PLC inhibitor U-73122. The catecholamine response to 10(-8) mol/liter orexins A and B was abolished by either U-73122 or the PKC antagonist calphostin C and was unaffected by the adenylate cyclase inhibitor SQ-22536 and the PKA inhibitor H-89. Collectively, these findings suggest that orexins stimulate catecholamine secretion from human pheochromocytomas, acting through OX2-R coupled to the PLC-PKC signaling pathway.

Adrenal Gland Neoplasms↗

PubMed2001

Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade.

Orexins A and B are two hypothalamic peptides that increase food intake and body weight and probably play a role in the sleep regulation. They act through two subtypes of G protein-coupled receptors, called OX1-R and OX2-R. OX1-R selectively binds orexin-A, whereas OX2-R is nonselective for both orexins. Orexins did not affect the in vitro secretion of either catecholamine or aldosterone from human adrenals. Conversely, orexin A, but not orexin B, concentration dependently increased basal cortisol secretion from dispersed adrenocortical cells; the maximal effective concentration was 10(-8) mol/L. Orexin A (10(-8) mol/L) enhanced the cortisol response to maximal effective concentrations (10(-9) mol/L) of angiotensin II and endothelin-1, but only to low concentrations of ACTH (10(-12)/10(-11) mol/L). Orexin A (10(-8) mol/L) increased basal cAMP release by dispersed adrenocortical cells, and the effect was blocked by the adenylate cyclase inhibitor SQ-22536. The cortisol response to 10(-8) mol/L orexin A was unaffected by the ACTH receptor antagonist corticotropin-inhibiting peptide, but was abolished by either SQ-22536 or the protein kinase A inhibitor H-89. RT-PCR demonstrated high levels of OX1-R messenger ribonucleic acid and very low levels of OX2-R messenger ribonucleic acid in human adrenal zona fasciculata-reticularis and adrenal medulla. Collectively, our findings suggest that orexins selectively stimulate glucocorticoid secretion from human adrenocortical cells, acting through OX1-R coupled with the adenylate cyclase-dependent signaling pathway.

Adenine↗

PubMed2001

Cortisol-secreting adrenal adenomas express 11beta-hydroxysteroid dehydrogenase type-2 gene yet possess low 11beta-HSD2 activity.

BACKGROUND: 11beta-hydroxysteroid dehydrogenase Type-2 (11beta-HSD2) is an unidirectional enzyme that catalyzes the conversion of glucocorticoid hormones cortisol and corticosterone (B) into their corresponding inactive forms, cortisone, and 11-dehydrocorticosterone (DH-B). We have provided evidence that 11beta-HSD2 is expressed as messenger RNA (mRNA) and protein in human adrenocortical cells, where its activity is inhibited in vitro by the main glucocorticoid agonists, adrenocorticotropic hormone (ACTH) and angiotensin-II. It seemed worthwhile, therefore, to study the gene expression and activity of 11beta-HSD2 in cortisol-secreting adrenocortical adenomas. METHODS: Three adrenal adenomas that produced Cushing syndrome were recruited. Three normal adrenal glands were obtained from patients who underwent unilateral nephrectomy with ipsilateral adrenalectomy for renal cancer. 11beta-HSD2 gene expression was studied by reverse transcriptionpolymerase chain reaction (RT-PCR) in adenoma and normal adrenocortical tissue. Cortisol, B, cortisone, and DH-B production by adenoma and adrenal slices in vitro was assayed by quantitative high-performance liquid chromatography (HPLC), and the activity of 11beta-HSD2 was evaluated by measuring the conversion of [3H]-cortisol to [3H]-cortisone. RESULTS: RT-PCR allowed the detection of the 11beta-HSD2 mRNA in the three adrenal adenomas and normal adrenal cortices examined. Under basal conditions, adenoma slices secreted higher amounts of cortisol and B, but markedly lower amounts of cortisone and DH-B than adrenal slices. ACTH raised cortisol and B production from both specimens, and it lowered cortisone and DH-B yield. The level basal conversion of [3H]-cortisol to [3H]-cortisone was notably less in adenomas than in adrenals, and ACTH decreased it in both tissues. CONCLUSIONS: Collectively, our findings indicate that cortisol-secreting adrenal adenomas express the 11beta-HSD2 gene, but the activity of the enzyme is suppressed in adenomas when compared with the normal adrenal cortex. We advance the hypothesis that the elevated local concentration of steroid hormones that occur in adenomas down-regulates 11beta-HSD2 activity, thereby contributing to their abnormal steroidogenic function.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2001

Signaling pathways involved in the A and B receptor-mediated cortisol secretagogue effect of endothelins in the human adrenal cortex.

Endothelins (ETs) are a family of 21-amino acid hypertensive peptides, which together with their receptors ETA and ETB are expressed in human adrenal cortex. Evidence has been provided that ETs exert a potent secretagogue effect on human adrenocortical cells, acting through both ETA and ETB receptors. Therefore, it seemed worthwhile to study the signaling cascades mediating the cortisol secretagogue effect of the two receptor subtypes. Normal adrenal glands were obtained from consenting patients undergoing unilateral nephrectomy with ipsilateral adrenalectomy for renal cancer. Dispersed zona fasciculata-reticularis (ZF/R) cells were obtained by collagenase digestion and mechanical disaggregation. The selective activation of ETA and ETB receptors was obtained by exposing dispersed cells to ET-1 plus the ETB receptor antagonist BQ-788 and to the selective ETB receptor agonist BQ-3020, respectively. ETA and ETB receptors about equally contributed to the cortisol response of dispersed ZF/R cells to ETs. The phospholipase (PL) C inhibitor U-73122 abolished ETA-mediated secretory response, but only partially prevented the ETB-mediated one. The phosphatidylinositol 3-kinase inhibitor wortmannin and the protein kinase (PK) C inhibitor calphostin-C significantly blunted the secretory responses ensuing from the activation of both receptor subtypes, while the Ca(2+)-channel blocker nifedipine was ineffective. The ETB receptor-, but not the ETA receptor-mediated cortisol response was partially reversed by the cyclooxygenase (COX) inhibitor indomethacin, which when added together with U-73122 abolished it. The inhibitors of adenylate cyclase, PKA, tyrosine kinase and lipoxygenase did not affect the secretory response to the activation of either receptor subtype. ETA-receptor activation raised inositol triphosphate (IP3) production from dispersed ZF/R cells, while ETB-receptor stimulation enhanced both IP3 and prostaglandin-E(2) production. Collectively, our findings indicate that ETs stimulate cortisol secretion from human ZF/R cells, acting through ETA receptors exclusively coupled with PLC/PKC-dependent pathway and ETB receptors coupled with both PLC/PKC- and COX-dependent cascades.

Adenine↗

PubMed2001

Expression of adrenomedullin and its receptors in the human adrenal cortex and aldosteronomas.

Adrenomedullin (ADM) is a hypotensive peptide, that derives from the proteolytic cleavage of pro(p)ADM and acts through at least two subtypes of receptors, called L1-receptor (L1-R) and calcitonin receptor-like receptor (CRLR). CRLR may function as a calcitonin gene-related peptide (CGRP) or a selective ADM receptor depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of proteins, referred to as receptor-activity-modifying proteins (RAMPs). Although adrenal cortex is known to be one of the main target organs of ADM, its expression of the ADM and its receptor has not yet been extensively investigated. Reverse transcription (RT)-polymerase chain reaction (PCR) revealed the expression of the pADM and peptidyl-glycine alpha-amidating monooxigenase (PAM) genes in four human adrenal cortexes and four aldosteronomas. Since PAM is the enzyme that converts immature ADM to the mature and active form, these findings suggest that the two tissues are able to produce ADM. RT-PCR also demonstrated high levels of L1-R mRNA and relatively low levels of CRLR mRNA, as well as the presence of specific mRNAs for the three RAMPs, thereby indicating that human adrenal cortex and aldosteronomas are provided with the two subtypes of classic ADM receptors. In conclusion, our investigation provides the first evidence that human adrenal cortex and aldosteronomas express the ADM system, that may play a role in the paracrine or autocrine control of their functions.

Adrenal Cortex↗