Multiple vertebral compression fractures in a human immunodeficiency virus-positive patient with glucocorticoid-induced Cushing syndrome treated with percutaneous vertebroplasty: a case report.

The authors present a rare case of multiple vertebral compression fractures in a young female with iatrogenic glucocorticoid-induced Cushing syndrome and concomitant human immunodeficiency virus (HIV) infection. Both long-term steroid use and HIV infection may lead to osteopenia or even osteoporosis. Multiple vertebral fractures in young patients are very uncommon and should alert the examiner to investigate any underlying cause. Treatment choices include pharmacological agents such as bisphosphonates or parathyroid hormone and even surgical interventions such as percutaneous vertebroplasty.

Predictive factors for early failure of transarterial embolization in blunt hepatic injury patients.

AIM: To evaluate the early success of transarterial embolization (TAE) in patients with traumatic liver haemorrhage and to determine independent factors for its failure. MATERIALS AND METHODS: From January 2009 to December 2012, TAE was performed in 48 patients for traumatic liver haemorrhage. Their medical charts were reviewed for demographic information, pre-TAE vital signs and laboratory data, injury grade, type of contrast medium extravasation (CME) at CT, angiography findings, and early failure. "Early failure" was defined as the need for repeated TAE or a laparotomy for hepatic haemorrhage within 4 days after TAE. Variables were compared between the early success and early failure groups. Variables with univariate significance were also analysed using multivariate logistic regression for predictors of early failure. RESULTS: Among 48 liver TAE cases, nine (18.8%) were early failures due to liver haemorrhage. Early failure was associated with injury grade (p = 0.039), major liver injury (grades 4 and 5; p = 0.007), multiple CMEs at angiography (p = 0.031), incomplete TAE (p = 0.002), and elevated heart rate (p = 0.026). Incomplete embolization (OR = 8; p = 0.042), and heart rate >110 beats/min (bpm; OR = 8; p = 0.05) were independent factors for early failure of TAE in the group with major liver injuries. CONCLUSION: Major hepatic injury is an important factor in early failure. Patients with a heart rate >110 bpm and incomplete embolization in the major injury group have an increased rate of early failure. The success rate of proximal TAE was comparable to that of the more time-consuming, superselective, distal TAE.

Monoamine oxidase deficiency in males with an X chromosome deletion.

Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

Nonopsonic antibodies in cystic fibrosis. Pseudomonas aeruginosa lipopolysaccharide-specific immunoglobulin G antibodies from infected patient sera inhibit neutrophil oxidative responses.

Antibody opsonins from cystic fibrosis (CF) patients were investigated using nonmucoid and mucoid lipopolysaccharide (LPS) immunotype 1 Pseudomonas aeruginosa as bacterial ligands and PMN phagocytes. CF sera were compared to normal sera, polyvalent PA LPS hyperimmune globulin, and isotype switch variant monoclonal antibodies (MAbs) specific for type 1 PA LPS. Sera from PA-infected CF patients (CF PA+) had elevated levels of PA LPS and alginate IgG antibodies and promoted significantly greater antibody-dependent PMN chemiluminescence responses than sera from uninfected CF patients (CF PA-) or normal human sera (NHS). After adjustment for autologous IgG PA LPS antibody content, however, CF PA+ sera had less antibody-dependent opsonic activity than sera from CF PA- patients (P less than 0.025) or NHS (P less than 0.0025), suggesting qualitative opsonic defects of IgG PA LPS antibodies in CF PA+ sera. Antigen-specific immunoprecipitation of PA LPS antibodies enhanced opsonization by 40% of CF PA+ sera while uniformly reducing that from CF PA- sera (P less than 0.01), indicating LPS-specific nonopsonic antibodies in some CF PA+ sera. Alginate antibodies were not critical opsonins in most uninfected CF patient sera. PA LPS IgG antibodies isolated by immunoaffinity chromatography from NHS, hyperimmune globulin, and CF PA- sources were opsonic and had greater activity at equal antigen-binding concentration than identical antibodies isolated from infected CF patients (P less than 0.01-0.05); the majority of isolates from CF PA+ sera did not promote PMN oxidative responses above nonopsonic baseline. A potential isotypic basis for these findings was supported by differences in PMN responses to PA opsonized with MAbs of identical specificity but differing isotypes. PA LPS-specific IgG antibodies inhibiting PMN oxidative responses in infected patient sera demonstrate antigen-specific immunomodulation of host responses by chronic bacterial parasitism in CF, which may play a role in the pathophysiology of lung disease.

The feasibility and efficacy of laparoscopic repair for chronic traumatic diaphragmatic herniation: introduction of a novel technique with literature review.

PURPOSE: Traumatic diaphragm rupture is a rare trauma that is easily overlooked. A missed diagnosis would result in chronic traumatic diaphragmatic herniation (CTDH). Surgical repair is the standard treatment that is conventionally performed by laparotomy or thoracotomy. Laparoscopic repair has been reported, but its efficacy remains controversial. In this study, we present our novel technique and experience of laparoscopic repair of CTDH and analyze the feasibility and effectiveness of this procedure. METHODS: We conducted a prospective collection with retrospective review of patients with CTDH treated at Chang Gung Memorial Hospital, Taiwan, from 2000 to 2013. The demographic characteristics, surgical procedure, perioperative results, length of hospital stay (HLOS) and follow-up were record and analyzed. RESULTS: There were 114 patients with traumatic diaphragm hernia, and 24 of them had CTDH with a mean age of 54.9 ± 13.3 years. The HLOS was 15.08 ± 8.17 days. Regarding the surgical method used, 19 patients had open surgery, and 5 patients underwent laparoscopic surgery. The demographic distribution, trauma mechanism, location and size of CTDH were comparable. In the laparoscopic group, the patients had a shorter median HLOS (6 days) than in the open surgery group (16 days; p = 0.002). There was no mortality or recurrence in both groups. CONCLUSIONS: In this study and literature review, patients had laparoscopic repair with a smooth recovery. Laparoscopy provides good surgical exposure, allowing easy repositioning of the herniated content and a smooth repair of the defect without the morbidity of laparotomy. For CTDH, with caution, we can apply this technique with an acceptable result.

Biochemistry and genetics of monoamine oxidase.

This chapter reviews the two mitochondrial flavin containing isozymes of monoamine oxidase. Section 1, "Biochemistry" discusses assays, substrates and inhibitors, phylogenic and tissue distribution, interactions with lipids, nutritional studies, protein structure, kinetic and chemical mechanistic proposals, and biosynthesis. Section 2, "Inheritance" discusses possible genes involved in expression, genetic studies of platelet MAO-B and fibroblast MAO-A, and chromosomal location. Section 3, "Molecular Genetics" reviews the cloning of their cDNAs, their intra- and interspecies homology and structural inferences made from deduced amino acid sequences. Section 4, "Regulation" gives an overview of levels in development and aging, and effect of drugs. The final section 5, "Role in Human Disease" discusses physiological function and effects of altered levels in humans and animal models including complete absence due to a submicroscopic chromosomal deletion in several human patients.

Alcohol dehydrogenase and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines.

Previous population association studies have indicated that certain alleles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes may reduce the risk of alcoholism in Oriental populations. In this report we determined the genotypes for three genes, ADH2, ADH3, and ALDH2 among subjects with alcohol dependence (n = 159) and ethnically matched normal controls (n = 149) for the four largest aboriginal groups (Atayal, Ami, Bunun, and Paiwan) in Taiwan. The ethnicity matching used in this study was feasible because there are still few intergroup marriages between these aboriginal groups. On a group level, the rare frequencies of ALDH2*2, the inactive allele of ALDH2, among these aborigines may account partially for their vulnerability to alcohol use disorders. On an individual level, however, the genotypes controlling alcohol metabolism did not account for intragroup differences in vulnerability to alcoholism except in the case of ADH2 for the Ami ethnic group.

Association of monoamine oxidase A alleles with alcoholism among male Chinese in Taiwan.

OBJECTIVE: The role of monoamine oxidase (MAO) in alcoholism was assessed by genetic association studies separately in five ethnic groups in Taiwan. METHOD: Restriction fragment length polymorphisms (RFLP) and dinucleotide repeat polymorphisms (DNRP) were used to determine MAOA and MAOB alleles in male alcoholic patients and nonalcoholic comparison subjects among Han Chinese and four aboriginal groups. RESULTS: Significant associations of alcohol dependence with MAOA alleles (RFLP and DNRP) were found among the Han Chinese, but not among the aboriginal groups. No significant association with MAOB DNRP alleles was found in any group. CONCLUSIONS: Genetic heterogeneity may underlie alcoholism among different ethnic groups in Taiwan, and MAOA mutations may play a role in susceptibility to alcoholism among Han Chinese.

Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model.

OBJECTIVE: To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension. DESIGN: Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors. MATERIALS AND METHODS: Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension. RESULTS: Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet

Mutational analysis of the human MAOA gene.

The monoamine oxidases (MAO-A and MAO-B) are the enzymes primarily responsible for the degradation of amine neurotransmitters, such as dopamine, norepinephrine, and serotonin. Wide variations in activity of these isozymes have been reported in control humans. The MAOA and MAOB genes are located next to each other in the p11.3-11.4 region of the human X chromosome. Our recent documentation of an MAO-A-deficiency state, apparently associated with impulsive aggressive behavior in males, has focused attention of genetic variations in the MAOA gene. In the present study variations in the coding sequence of the MAOA gene were evaluated by RT-PCR, SSCP, and sequencing a mRNA or genomic DNA in 40 control males with > 100-fold variations of MAO-A activity, as measured in cultured skin fibroblasts. Remarkable conservation of the coding sequence was found with only 5 polymorphisms observed. All but one of these were in the third codon position and thus did not alter the deduced amino acid sequence. The one amino acid alteration observed, lys --> arg, was neutral and should not affect the structure of the protein. This study demonstrates high conservation of coding sequence in the human MAOA gene in control males, and provides primer sets which can be used to search genomic DNA for mutations in this gene in males with neuropsychiatric conditions.

Dopamine D2 receptor gene and alcoholism among four aboriginal groups and Han in Taiwan.

Previous studies examining the putative association between DRD2 TaqI A1 and alcoholism have produced conflicting results. Major critiques of such studies include potential confounding arising from population admixture by inappropriate selection of controls, failure to screen out substance abusers from controls, and the failure to assess the severity of alcoholics. To address these issues, we compared the allelic frequency of two polymorphisms of DRD2, TaqI A and NcoI, among severe alcoholics and their ethnically matched nonalcoholic controls within four major aboriginal groups and Han (Chinese) in Taiwan. The sample of alcoholics and controls examined for the five groups included 36 and 31 (Atayal), 24 and 23 (Ami), 58 and 58 (Bunun), 35 and 35 (Paiwan), and 50 and 66 (Han). A borderline association between TaqI A1 and alcoholism among the Ami (P = 0.08) and an association between NcoI N1 and alcoholism among Han (P = 0.01) were found. Results of haplotype analysis further confirm that the frequency of haplotype A1N1 was higher in alcoholics than in controls for the Ami (P = 0.01) and Han (P = 0.03). If controls with tobacco abuse were excluded from the analysis, the results remained unchanged. Severity in medical complications of alcohol dependence with withdrawal symptoms was not associated with higher prevalence of DRD2 TaqI A1 or NcoI N1 alleles. The absence of an association between DRD2 and alcoholism among the three aboriginal groups suggests either a higher rate of phenocopies among aboriginal alcoholics or genetic heterogeneity in the susceptibility to alcoholism.

Screen for MAOA mutations in target human groups.

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.

Search for mutations near the alternatively spliced 8-amino-acid exon in the GABAA receptor gamma 2 subunit gene and lack of allelic association with alcoholism among four aboriginal groups and Han Chinese in Taiwan.

The alternatively spliced 8-amino-acid exon for the GABAA receptor gamma2 subunit gene (GABRC2) has been postulated to mediate behavioral actions of alcohol. A rapid search for splice-junction mutations near the 8-amino-acid exon using restriction enzymes which normally recognize sequences near or in the exon gave negative results among 217 alcoholics in four aboriginal groups (Ami, Atayal, Bunun and Paiwan) and Han Chinese in Taiwan. The role of the GABRC2 gene in alcoholism was further assessed by a comparison of allelic frequencies revealed by a NciI RFLP between case and control groups. No significant association of alcohol dependence with GABRC2 alleles was observed. These results suggest that the GABRC2 gene probably does not play an essential role in predisposition to alcoholism in the sample population.

Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (AIE1, AIE2) related to yeast and fly chromosome segregation regulators.

We have analyzed the general protein kinase expression profile in mouse sperm and eggs. A total of 41 different kinases were identified. In this study, we describe two novel protein kinases, designated AIE1 (mouse) and AIE2 (human), which share high amino acid identities with the serine/threonine (S/T) kinase domain of yeast Ip11, fly aurora, and frog Eg2. Mutations in Ip11 and aurora have been reported to cause abnormal chromosome segregation and centrosome separation. Both AIE1 and AIE2 contain a typical S/T kinase domain (251 aa) flanked by a short polypeptide at both ends. Two other AIE-related kinases (STK-1 and IAK1/Ayk1) were also identified in mature mouse oocytes. The central kinase domain of AIE1 revealed 77.6% and 66.3% identity with that of STK-1 and IAK1/Ayk1, but much less homology was found in the sequence outside the kinase domain. Northern blot analysis revealed that both AIE1 and AIE2 are specifically expressed in testis, whereas STK-1 and IAK1/Ayk1 are expressed in many tissues rich in proliferating cells. An in vitro kinase assay showed that AIE1 can phosphorylate casein, AIE1 itself, and an uncharacterized cellular protein (p16). The kinase activity of AIE1 can be destroyed by heat inactivation. In summary, we suggest that AIE is a new member of the S/T kinase family, which may be regulated in a fashion distinct from other AIE-related kinases.

Genetic polymorphisms of the promoter region of dopamine D2 receptor and dopamine transporter genes and alcoholism among four aboriginal groups and Han Chinese in Taiwan.

This study aims to examine the relationship between the functional polymorphism at the promoter region of the dopamine D2 receptor (DRD2) gene (i.e. -141C Ins/Del) and variable number of tandem repeat polymorphism at the 3' untranslated region of the dopamine transporter (DAT) gene (SLC6A3) with alcoholism in a case-control study. The cases (n = 203) were alcohol dependents with withdrawal symptoms, and the controls (n = 213) were sex- and ethnicity-matched individuals who were screened to exclude those with alcohol problems among four aboriginal groups (Atayal, Ami, Bunun, and Paiwan) and Han Chinese in Taiwan. To control for potential confounding factors, we excluded tobacco abusers from control subjects in part of the analysis and compared the distribution of the genetic polymorphisms in alcoholics with severe medical complications versus those with less severe medical complications. There were no differences in allele and genotype frequencies of these two distinct genetic markers between alcoholics and control subjects in these five different ethnic groups. There was no significant linkage disequilibrium between the -141C polymorphism and two other DRD2 polymorphisms (TaqI A and NcoI). The results remained unchanged when cases were limited to alcoholics with more severe medical complications or when tobacco abusers were excluded from control subjects. The results suggest that both the DRD2 promoter region and the DAT gene do not play a significant role in conferring vulnerability to alcoholism.

Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETA receptors.

The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake (ISGU) in rat adipocytes was investigated. Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley rats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agonist for ETC receptors, to displace [125I]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 >> ET-3, indicating that the primary receptors involved belonged to the ETA subtype. At an equal concentration of 1 micromol/L, BQ-610, a selective ETA antagonist, displaced [125I]ET-1 from binding to fat cells, whereas IRL-1038, a selective ETB antagonist, did not. Using [3H]2-deoxy-D-1-glucose ([3H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective. Northern blot analysis of adipocyte receptors showed abundant mRNA for ETA, but no ETB subtype. These results clearly demonstrate that ETA is the predominant receptor in rat adipocytes.

Anti-arthropod saliva antibodies among residents of a community at high risk for Lyme disease in California.

The role of the western black-legged tick (Ixodes pacificus) versus that of other potential arthropod vectors in the epidemiology of Lyme disease was evaluated by determining the prevalence of anti-arthropod saliva antibodies (AASA) among residents (n = 104) of a community at high-risk (CHR). Salivary gland extracts prepared from I. pacificus, the Pacific Coast tick (Dermacentor occidentalis), the western cone-nose bug (Triatoma protracta), and the western tree-hole mosquito (Aedes sierrensis) were used as antigens in an ELISA. Sera from 50 residents of the San Francisco Bay region in northern California and 51 residents of Imperial County in southern California served as comparison groups. The prevalence of AASA ranged from 2% for A. sierrensis to 79% for I. pacificus in study subjects, 0% for D. occidentalis to 36% for I. pacificus among residents of the San Francisco Bay region, and 6% for I. pacificus to 24% for A. sierrensis in residents of Imperial County. The associations between AASA and demographic factors, potential risk factors, probable Lyme disease, and seropositivity for Borrelia burgdorferi were assessed for 85 members of the CHR. Seropositivity for I. pacificus and B. burgdorferi were significantly correlated, the relative risk of seropositivity to B. burgdorferi was about 5 (31% versus 6%) for subjects who were seroreactive to I. pacificus, nearly every individual who was seropositive for B. burgdorferi had elevated levels of antibodies to I. pacificus, and the mean titer for antibodies to I. pacificus was significantly higher for subjects seropositive versus those seronegative for B. burgdorferi. Together, these findings support the widely held belief that I. pacificus is the primary vector of B. burgdorferi for humans in northern California, and they demonstrate the utility of the AASA method as an epidemiologic tool for studying emerging tick-borne infections.

Pseudomonas hyperimmune globulin passive immunotherapy for pulmonary exacerbations in cystic fibrosis.

We studied the effect of an intravenously administered gamma globulin [Ps-ivIG] enriched fivefold over conventional ivIG for Pseudomonas aeruginosa lipopolysaccharide [PA LPS] antibodies on ten patients with cystic fibrosis [CF] aged 19-32 years during hospitalization for pulmonary deterioration. All were colonized with greater than or equal to 1 PA phenotype resistant to all antibiotics at the time of admission and they received 500 mg/kg Ps-ivIG intravenously as a single dose in addition to conventional treatment, including antibiotics and chest physiotherapy. No adverse effects occurred. Circulating immune complexes and complement levels remained unchanged from baseline. Serum levels of anti-PA LPS IgG, as measured by ELISA for eight PA LPS immunotypes, increased to 244 +/- 65% (mean +/- SE) of baseline levels 1 hour post-infusion (P less than 0.01), remained significantly elevated during a mean hospital stay of 17 days, and returned to near baseline by follow-up 4 weeks after hospital discharge. Plasma half-life and clearance values were similar to those of other subjects receiving conventional ivIG. Sputum PA density declined from 3.0 to 1.2 x 10(8) cfu/mL 1 week post-infusion (P approximately equal to 0.05), and returned to baseline at follow-up. Serum anti-PA opsonic activity increased after infusion (P less than 0.01), but returned to baseline by 72 hours. Clinical scores improved from admission to discharge (P less than 0.005) without decline at follow-up. Forced vital capacity [FVC] and forced expiratory volume in one second [FEV1] increased from admission to discharge (P less than 0.01 and P less than 0.05, respectively) without decline at follow-up. Using autologous historical control data, standard hospital therapy without Ps-ivIG resulted in no improvement in FVC or FEV1, and a subsequent decline in these parameters (P less than 0.05 for each) during a similar follow-up period. This occurred despite the fact that half the patients did not have antibiotic-resistant PA on the control admission. We conclude that Ps-ivIG is a safe adjunctive therapy for pulmonary exacerbations in moderately ill cystic fibrosis patients colonized with resistant PA, and may be associated with both greater and more prolonged improvement in pulmonary function than standard therapy alone.

The stimulatory effect of vasoactive intestinal peptides on the cortisol production of guinea pig Zona fasciculata cells: an extra-ACTH regulatory model of the adrenocortical function.

The effect of vasoactive intestinal peptide (VIP) on cortisol production was studied in a primary culture enriched with guinea pig Zona Fasciculata (ZF) cells. In ZF cells, VIP stimulates cortisol secretion and enhances the steroidogenic action of ACTH. Compared to ACTH on an equal molar basis, the cortisol-stimulatory effect of VIP is at least 10-fold less potent. As VIP exhibits a wide range of biological actions with widespread distribution in the body, the steroidogenic action of VIP on the adrenal glands is not tissue-specific. There are VIP receptors in ZF cells. With the aid of a VIP receptor antagonist, we found that ACTH and VIP mutually bind each other's receptors with an affinity-ranking order of ACTH > VIP receptor antagonist > VIP. VIP stimulates cortisol production most likely through the cyclic AMP (cAMP) signaling pathway. Both ACTH receptors and the VIP receptors bind VIP receptor antagonist more avidly than VIP, but the bindings do not lead to a consequential effect on cAMP production and cortisol secretion. However, the VIP receptor antagonist counteracted ACTH and VIP to lower both cAMP and cortisol production. In addition, ASIF and BNP-32, which are the proven ACTH receptor antagonists, reduced the cortisol-stimulatory effect of ACTH and VIP. These results suggest that besides ACTH, VIP be an important factor in regulating the cortisol secretion from the adrenal cortex at the site of ACTH receptors. In cases with hypercortisolemia being detected concomitantly with normal or low ACTH levels, we may need to investigate the influential role of VIP.