Long-term nutritional impact of sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) has become a predominant bariatric procedure throughout the world. However, the long-term nutritional impact of this procedure is unknown. OBJECTIVES: To describe the nutritional deficiencies before and after SG and to analyze the influence of baseline weight on nutritional status. SETTING: University-affiliated tertiary care center. METHODS: All patients who underwent SG as a standalone procedure between 2008 and 2012 were included in this study. Patients were given multivitamin supplementation. Data were obtained from our prospectively maintained electronic database and are reported as mean ± standard deviation and percentage. Bivariate analyses were conducted to evaluate the influence of selected variables on outcomes. RESULTS: The mean age of the 537 patients was 48.0 ± 11.3 years, with an initial body mass index of 48.1 ± 8.7 kg/m2. Excess weight loss and total weight loss were 56.2% and 28.0% at 1 year and 43.0% and 21.1% at 5 years, respectively (P<.0001). Percentage of follow-up was 74% at 5 years (n = 79). The mean follow-up time was 34.3 ± 17.2 months. Hypoalbuminemia was present in 1.1% preoperatively and 4.2% at 5 years (P = .0043), low ferritin levels in 8.6% and 37.8% (P<.0001), low vitamin B12 in 30.3% and 16.4% (P<.0001), low vitamin D 63.2% and 24.3% (P<.0001), and hyperparathyroidism in 23.4% and 20.8% (P<.0001). There was no significant difference in the prevalence of anemia over time (P = 0.4301). The prevalence of vitamin A insufficiency peaked from 7.9% preoperatively to 28.7% at 3 months (P<.0001) and returned to baseline thereafter. Baseline weight was negatively correlated with vitamin B12 and vitamin D. CONCLUSION: Nutritional deficiencies are common in patients with morbid obesity before and after surgery. Preoperative supplementation and long-term nutritional follow-up are required to prevent nutritional deficiencies.

Laparoscopic sleeve gastrectomy: with or without duodenal switch? A consecutive series of 800 cases.

BACKGROUND: Sleeve gastrectomy (SG) was originally performed as the restrictive and acid-reducing part of a biliopancreatic diversion with duodenal switch (BPD-DS). It is now recognized as a stand-alone procedure, but direct comparison between the two procedures is still lacking. The goal of this study is to compare the outcomes of the two procedures and their respective impact on obesity-related comorbidities. METHODS: All patients who had a laparoscopic SG (n = 378) or a laparoscopic BPD-DS (n = 422) before 10/2011 were included in this study (n = 800). Data were obtained from our prospectively maintained electronic database and are reported as mean ± standard deviation comparing SG with BPD-DS patients. RESULTS: SG patients were older (48 ± 11 vs. 40 ± 10 years, p < 0.001) with a higher prevalence of comorbidities (type 2 diabetes mellitus in 51 vs. 37%; hypertension 62 vs. 49%; sleep apnea 63 vs. 51%; all p < 0.001). Initial BMI was 48 ± 9 vs. 48 ± 6 (p = 0.8). There was one 30-day mortality in the BPD-DS group, from a pulmonary embolism, for an overall mortality rate of 0.13%. Thirty-day complications occurred in 6 vs. 8% of patients (p = 0.2), including gastric leaks in 4 (1%) vs. 0 patients (p = 0.049). Mean follow-up was 29 ± 10 months. Excess weight loss was 45 ± 14 vs. 62 ± 15% at 6 months, 53 ± 18 vs. 81 ± 14% at 12 months, 53 ± 23 vs. 87 ± 15% at 18 months, 50 ± 19 vs. 86 ± 15% at 24 months and 51 ± 24 vs. 83 ± 16% at 36 months (p < 0.05 for all time points). The surgery induced the remission of type 2 diabetes mellitus in 56 vs. 90% of patients, hypertension in 54 vs. 76% and sleep apnea in 43 vs. 74% (all p < 0.05). In type 2 diabetic patients, fasting plasma glucose decreased by -1.9 mmol/l after SG vs. -2.9 mmol/l after BPD-DS (p < 0.05) and hemoglobin A1C by -1.1 vs. -1.9% (p < 0.05). CONCLUSION: SG results in a significant 3-year weight loss and remission of comorbidities. BPD-DS provides further improvement of associated comorbidities and can be an option for the management of insufficient weight loss or residual comorbidities following SG.

DUSP1 Gene Polymorphisms Are Associated with Obesity-Related Metabolic Complications among Severely Obese Patients and Impact on Gene Methylation and Expression.

The DUSP1 gene encodes a member of the dual-specificity phosphatase family previously identified as being differentially expressed in visceral adipose tissue (VAT) of severely obese men with versus without the metabolic syndrome. Objective. To test the association between DUSP1 polymorphisms, obesity-related metabolic complications, gene methylation, and expression levels in VAT. Methods. The DUSP1 locus and promoter region were sequenced in 25 individuals. SNPs were tested for association with obesity-related complications in a cohort of more than 1900 severely obese individuals. The impact of SNPs on methylation levels of 36 CpG sites and correlations between DNA methylation and gene expression levels in VAT were computed in a subset of 14 samples. Results. Heterozygotes for rs881150 had lower HDL-cholesterol levels (HDL-C; P = 0.01), and homozygotes for the minor allele of rs13184134 and rs7702178 had increased fasting glucose levels (P = 0.04 and 0.01, resp.). rs881150 was associated with methylation levels of CpG sites located ~1250 bp upstream the transcription start site. Methylation levels of 4 CpG sites were inversely correlated with DUSP1 gene expression. Conclusion. These results suggest that DUSP1 polymorphisms modulate plasma glucose and HDL-C levels in obese patients possibly through alterations of DNA methylation and gene expression levels.

A polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals.

A previous expression profiling of visceral adipose tissue (VAT) revealed that the immune response gene interferon-gamma-inducible protein 30 (IFI30) gene was 1.72-fold more highly expressed in non-diabetic severely obese men with the metabolic syndrome as compared to those without. Given the importance of low-grade inflammation in obesity-related metabolic complications, we hypothesized that variants in the IFI30 gene are associated with cardiovascular disease (CVD) risk factors. A detailed genetic investigation was performed at the IFI30 locus by sequencing its promoter, exons and intron-exon junction boundaries using DNA of 25 severely obese men. Among the 21 sequence-derived single-nucleotide polymorphisms (SNPs), 5 tagged SNPs (covering 100% of the common SNPs identified) were genotyped in two independent samples of severely obese patients (total n = 1,283). Using a multistage experimental design, chi-square analyses and logistic regressions were performed to compare genotype frequencies and compute odds-ratios (OR) for low and high CVD risk groups (dyslipidemia, hyperglycemia/diabetes and hypertension). A significant association was observed with the non-synonymous SNP rs11554159 (p.R76Q), where GA individuals showed lower risk (OR = 0.67; P = 0.0009) for hyperglycemia/diabetes as compared to homozygotes for the major allele (GG). No association was observed between rs11554159 and VAT IFI30 mRNA levels (P = 0.81), and the expression levels were not correlated with fasting plasma glucose levels (P = 0.31) in 112 non-diabetic severely obese women. The localization of rs11554159 near the active site of IFI30 suggests a functional effect of this SNP. This study showed a novel association between rs11554159 (p.R76Q) polymorphism at the IFI30 locus and the risk of hyperglycemia/diabetes in severely obese individuals.

Collaboration between basic science researchers and bariatric surgeons is a win/win proposition: view from the chair.

Bariatric surgery in humans offers a window of opportunity to further our understanding of obesity and associated diseases. In the morbidly obese subjects, physiological disturbances are amplified and their extreme manifestations are more easily measured. The significant and predictable effects of bariatric surgery present a striking contrast to preoperative morbid conditions. The bariatric procedure is a reproducible therapy occurring at a precise time point; this facilitates the recording of preoperative and postoperative parameters over a short period of time, with some assurance that the contrasted conditions will confirm or disprove hypotheses with manageable numbers of subjects, thus providing an economy of means and efforts in a shorter time frame.

Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity.

BACKGROUND AND OBJECTIVES: By studying cardiometabolic risk factors in children born after maternal biliopancreatic diversion bariatric surgery (AMS) compared with those in children born before maternal surgery (BMS), we tested the hypothesis that significant maternal weight loss may modify obesity-related factors transmitted via the intrauterine environment. DESIGN: Anthropometry and fasting blood levels were studied in 49 mothers who had lost 36 +/- 1.8% body weight sustained for 12 +/- 0.8 yr and their 111 children (54 BMS and 57 AMS) aged 2.5-26 yr. RESULTS: AMS children had lower birth weight (2.9 +/- 0.1 AMS vs. 3.3 +/- 0.1 kg BMS, P = 0.003) associated with a reduced prevalence of macrosomia (1.8 AMS vs. 14.8% BMS, P = 0.03) with no difference in underweight. At the time of follow-up, AMS children exhibited 3-fold lower prevalence of severe obesity (11 vs. 35%, P = 0.004), greater insulin sensitivity (homeostasis model assessment of insulin resistance index 3.4 +/- 0.3 vs. 4.8 +/- 0.5, P = 0.02), improved lipid profile (cholesterol/high-density lipoprotein cholesterol 2.96 +/- 0.11 vs 3.40 +/- 0.18, P = 0.03; high-density lipoprotein cholesterol 1.50 +/- 0.05 vs. 1.35 +/- 0.05 mmol/liter, P = 0.04), lower C-reactive protein (0.88 +/- 0.17 vs. 2.00 +/- 0.34 microg/ml, P = 0.004), and leptin (11.5 +/- 1.5 vs.19.7 +/- 2.5 ng/ml, P = 0.005) and increased ghrelin (1.28 +/- 0.06 vs.1.03 +/- 0.06 ng/ml, P = 0.005) than BMS offspring (AMS vs. BMS, respectively, for all). CONCLUSIONS: This unique study of children aged 2.5-26 yr born before and after maternal antiobesity surgery demonstrated improvements in cardiometabolic markers sustained into adolescence, attributable to an improved intrauterine environment.

CYR61 polymorphisms are associated with plasma HDL-cholesterol levels in obese individuals.

We have recently characterized the transcriptome of the omental adipose tissue of non-diabetic, obese men with and without the metabolic syndrome (MS). The cysteine-rich protein 61 (CYR61) is one of the most differentially expressed genes between the groups and has been selected for a detailed molecular investigation. Direct sequencing of complete CYR61 gene revealed five polymorphisms with minor allele frequency >5% in the promoter region (rs 3753794, rs 3753793 and rs 2297140), intron 1 (rs 2297141) and intron 2 (IVS 2+50). Chi-square test and logistic regression were applied to test for association between CYR61 polymorphisms and the individual MS components in a cohort of 697 obese individuals. In men and women, rs 3753794 and rs 3753793 (r2 = 0.77) were associated plasma HDL-cholesterol levels (p = 0.016 and p = 0.008). Carriers of the A allele for rs 3753794 were more likely to have high plasma HDL-cholesterol levels (1.50-fold; p = 0.016), as compared with G/G homozygotes and the A/A homozygotes for rs 3753793 were more likely to exhibit low plasma HDL-cholesterol levels (1.56-fold; p = 0.008), as compared with C/C homozygotes. Furthermore, an association between IVS 2+50 polymorphism and HDL-cholesterol was found in women and in men analyzed separately (p = 0.002 and p = 0.038, respectively). These results suggest that CYR61 is a promising candidate gene for lipoprotein/lipid perturbations.

Effects of the biliopancreatic diversion on energy balance in the rat.

OBJECTIVE: This study was carried out to determine the effects of the biliopancreatic diversion (BPD), a bariatric surgery applied to the treatment of morbidly obese humans, on energy balance in rats. METHODS: BPD was performed on a group of male Wistar rats. Body weight and food intake were measured daily throughout the study. Feces were also collected to assess energy losses and the determination of digestible energy. Energy expenditure and body composition were also determined for the 50-day length of the protocol. On the day of killing, the brain, the entire intestinal tract and white and brown adipose tissues were collected and weighed. Expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the ARC nucleus were assessed by in situ hybridization. RESULTS: Marked changes in the regulation of energy balance were observed in the BPD-operated rats. A decrease in digestible energy and food intake coupled with an increase in the fecal energy density and protein fecal energy led to an important weight loss in the BPD-operated rats. This weight loss was observed in the loss of fat mass (specifically the white epididymal, inguinal, retroperitoneal and brown adipose tissues). The rats modified their food intake pattern to be able to potentially eat more during the entire day. An increase in the surfaces of all intestinal structures (muscular and mucosal layers) was observed in the BPD-operated rats. The NPY and AgRP expression in the brain were both shown to be greater in the BPD-operated rats than in the control animals. At the beginning of the study, the surgery led to an energy expenditure decrease, which, however, did not persist throughout the study despite the fact that BPD-operated rats exhibited persistent lower fat free masses. CONCLUSION: BPD led to a noticeable reduction in weight and fat gains in rats, which was in large part owing to a decrease in digestible energy intake led to by the gastrectomy, the intestinal malabsorption inherent to the surgery and to potentially a thermogenesis stimulation that occurred in the second end of the study. The reduction in energy gain occurs despite adaptations to thwart the intestinal malabsorption and the hunger signals from the central nervous system.

In vitro and in vivo contractile properties of the vastus lateralis muscle in males with COPD.

Peripheral muscle weakness is common in chronic obstructive pulmonary disease (COPD) but it is still under debate whether weakness is due to atrophy or contractile dysfunction. In vitro and in vivo contractile properties of the vastus lateralis muscle were studied in 16 patients with stable COPD (forced expiratory volume in one second 39 +/- 16% of predicted, age 67 +/- 4 yrs (mean +/- sD)) and nine sedentary control subjects. Isometric knee extensor strength was measured while mid-thigh muscle cross-sectional area (MTMCSA) was obtained using computed tomography. Muscle strips from the vastus lateralis obtained through open biopsy were rapidly suspended in an oxygenated Krebs-Ringer solution that was maintained at 35 degrees C with a pH of 7.40 to study their contractile properties. The isometric knee extensors strength/MTMCSA ratio was 0.50 +/- 0.08 versus 0.58 +/- 0.06 kg x cm(-2) for COPD and control subjects, respectively. The muscle bundle cross-sectional area (CSA) was 4.6 +/- 2.1 and 4.4 +/- 3.1 mm(-2), the length at which active tension was maximum was 15 +/- 4 and 15 +/- 3 mm, and maximal isometric peak forces normalised for CSA were 4.3 +/- 2.7 and 4.8 +/- 2.6 N x cm(-2) for COPD and control subjects, respectively. The force/frequency relationship tended to be shifted to the right in patients with COPD, meaning that a higher stimulation frequency was necessary to produce the same relative force. Patients with COPD had a lower proportion of type I fibre than controls (26 +/- 12% versus 39 +/- 11%) with reciprocal significant increase in type IIb fibre proportion (20+/-16% versus 8 +/- 4%). The proportion of type IIa fibres was similar between the two groups. These results suggest that the contractile properties of the vastus lateralis are preserved in patients with chronic obstructive pulmonary disease. Therefore, the reduction in the quadriceps strength in patients with chronic obstructive pulmonary disease cannot be explained on the basis of an alteration of the contractile apparatus.

Malabsorptive obesity surgery.

Biliopancreatic diversion is the only valuable surgical approach for changing intestinal absorption. It is efficient in producing appropriate permanent weight loss and has a considerable psychological advantage because it does not impose abnormal food restriction. It not only decreases caloric absorption, but it also directly improves insulin and lipid metabolism. The ideal technique for the construction of BPD is not yet established, but our current preference is for the duodenal switch type. BPD must be seen as a means to change an intolerable and untreatable disease to a tolerable and treatable one, with substantial improvement in quality of life.

Restoration of myoelectrical propagation across a jejunal transection using microsurgical anastomosis.

The aim of this study was to determine whether microsurgical anastomosis can restore propagation of jejunal pacesetter potentials (PPs) across a site of canine jejunal transection and preserve motility and transit in bowel distal to the transection. A complete jejunal transection with exact microsurgical anastomosis was performed in five dogs, while five dogs with intact jejunum and five dogs with complete transection and end-to-end conventional macrosurgical anastomosis were used as controls. Long-term recording electrodes and intraluminal, open-tipped pressure catheters were implanted in all dogs. The mean frequency of PPs decreased distal to the transection in both groups of transected dogs. However, aborad propagation of PPs across the anastomosis occurred episodically by 3 months in each dog that had a microsurgical anastomosis, but never occurred in any dog with a conventional macroanastomosis. Moreover, the motility and transit in bowel distal to the transection were unaltered in the dogs with a microsurgical anastomosis, whereas they decreased in the dogs with a macroanastomosis. The conclusion was that microsurgical anastomosis of transected canine jejunum restored episodic propagation of PPs across the anastomosis, and preserved motility and maintained transit in bowel distal to the anastomosis. The conventional macroanastomosis did none of these.

Liver pathology and the metabolic syndrome X in severe obesity.

The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of adipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbohydrate, lipid, and steroid metabolism, we investigated the relationships between liver pathology and the metabolic syndrome. Blood chemistry, anthropometry (waist/hip circumference ratio), and intraoperative routine knife biopsies of the liver were obtained in 551 (112 men) severely obese patients (body mass index, 47 +/- 9; mean +/- SD) undergoing antiobesity surgery. Steatosis was found in 86%, fibrosis in 74%, mild inflammation or steatohepatitis in 24%, and unexpected cirrhosis in 2% (n = 11) of the patients. The risk of steatosis was 2.6 times greater in men than in women (P < 0.0001). With each addition of 1 of the 4 components of the metabolic syndrome, elevated waist/hip ratio, impaired glucose tolerance, hypertension, and dyslipidemia, the risk of steatosis increased exponentially from 1- to 99-fold (P < 0.001). Fibrosis correlated with steatosis (r = 0.56; P < 0.0001), whereas patients with diabetes or impaired glucose tolerance had a 7-fold increased risk of fibrosis (P < 0.0001). Diabetes, steatosis, and age were all significant indicators of cirrhosis, whereas inflammation was only associated with age. We conclude that the metabolic syndrome via impaired glucose tolerance is strongly correlated with steatosis, fibrosis, and cirrhosis of the liver.

Biliopancreatic diversion (doudenal switch procedure).

The physiological principle underlying biliopancreatic diversion (BPD) is attractive. It decreases food absorption and particularly that of fat. It preserves normal eating habits and is compatible with a good quality of life. Because weight loss is not a function of an imposed aversion to eating, it is more appealing to patients. Data are accumulating showing that BPD can permanently cure morbid obesity in a majority of patients and is remarkably well tolerated. While long-term systemic side-effects from decreased absorption continue to raise concerns, available results have already shown that, within 20 years, metabolic disturbances are well tolerated while weight loss and quality of life are maintained. Vitamin and mineral replacement therapy and periodic monitoring are essential. The original procedure described by Scopinaro with subsequent modifications will be presented, focusing on the duodeno-ileal switch procedure.

Biliopancreatic diversion with duodenal switch.

In 1990 Scopinaro's technique of biliopancreatic diversion with distal gastrectomy (DG) and gastroileostomy was modified. A sleeve gastrectomy with duodenal switch (DS) was used instead of the distal gastrectomy; and the length of the common channel was made 100 cm instead of 50 cm. A questionnaire and a prescription for blood work were sent to 252 patients who underwent DG a mean 8.3 years ago (range 6-13 years) and 465 patients who underwent DS 4.1 years ago (range 1.7-6.0 years). The questionnaire response rate was 93%, and laboratory work was completed for 65% of both groups. The mean weight loss after DG was 37 +/- 21 kg and after DS 46 +/- 20 kg. There were fewer side effects after DS: The number of daily stools was lower (p < 0.0002), as was the prevalence of diarrhea (p < 0.01), vomiting (p < 0.001), and bone pain (p < 0.001). Greater benefits related to several aspects of life were reported after DS than DG (p < 0.0001). The mean serum levels of ferritin, calcium, and vitamin A were higher (p < 0.001), and parathyroid hormone was lower. The yearly revision rate for excessive malabsorption was 1.7% per year after DG and 0.1% per year after DS. The two procedures were equally efficient for treating co-morbid conditions such as diabetes, hypertension, and hypercholesterolemia. Biliopancreatic diversion with sleeve gastrectomy/duodenal switch and a 100-cm common limb was shown to produce greater weight loss with fewer side effects.

Ectopic jejunal pacemakers after jejunal transection and their relationship to transit.

The hypothesis was that orally moving pacesetter potentials distal to a site of jejunal transection and anastomosis would slow transit through jejunum containing them and that reoperation with excision of bowel containing these pacesetter potentials would restore transit to the control. In six conscious dogs with jejunal serosal electrodes for recording myoelectric activity and a jejunal perfusion/aspiration catheter for measuring transit, jejunal pacesetter potential frequency decreased distal to a midjejunal transection and anastomosis from 18.7 +/- 0.3 (SE) cycles/min (cpm) proximal to the site to 14.4 +/- 0.6 cpm distal to the site (P < 0.05). In addition, orally propagating pacesetter potentials occurred > 25% of the time in a 37 +/- 7 cm length of bowel distal to the site during fasting and after feeding. Transit through the segment with the orally moving pacesetter potentials was slowed during feeding (half time before and after transection, 7.7 +/- 1.1 and 13 +/- 2.0 min, respectively, P < 0.05). Resection of the segment with the abnormal pacesetter potentials shortened the length of bowel containing them to 24 +/- 2 cm (P > 0.05) and restored transit to the control. In conclusion, orally moving pacesetter potentials distal to a canine jejunal transection and anastomosis slowed transit through the segment of bowel containing them. Resection of the segment restored transit to the control.

Influence of proximal gastric vagotomy on canine gastric motility and emptying.

BACKGROUND: The aim was to determine the effect of proximal gastric vagotomy on proximal gastric tone, distal gastric motility, and gastric emptying in seven conscious dogs. METHODS AND RESULTS: Before vagotomy, insulin (1 unit/kg intravenously) caused a prompt decrease in proximal gastric tone measured with a barostat and a marked increase in distal gastric motility measured with a perfused, pressure-sensitive catheter, both of which were maximal at 30 minutes. Proximal gastric tone then returned to the control level during the ensuing 30 minutes, whereas the increase in distal gastric motility continued. Gastric emptying of an inert marker, polyethylene glycol, was unchanged by insulin. After vagotomy, insulin again caused a prompt decrease in proximal gastric tone, an increase in distal gastric motility, and no change in gastric emptying of marker, but the decrease in proximal gastric tone now persisted for the entire hour after administration of insulin. CONCLUSIONS: Relaxation of the proximal stomach is mediated by pathways not solely dependent on the proximal gastric vagal nerves, but the ability to regain proximal gastric tone is impaired by proximal vagotomy. In contrast, vagal drive to distal gastric motility and gastric antral emptying are preserved after proximal gastric vagotomy.

Nifedipine inhibits cholecystokinin-induced gallbladder contraction.

Nifedipine is a calcium channel blocker which results in relaxation of smooth muscle. Although it has been utilized clinically to treat cardiovascular disease, and more recently spastic disorders of the esophagus and colon, its effects on gallbladder contractility have not been clearly defined. We tested the effects of nifedipine on gallbladder contraction stimulated by cholecystokinin (CCK) in a conscious guinea pig model and in healthy human volunteers. Gallbladder contraction was measured in response to repeated injections of CCK before and after intravenous nifedipine given to groups of five guinea pigs in a dose of 100, 200, or 300 micrograms. Nifedipine virtually abolished spontaneous interdigestive gallbladder contractile activity and decreased resting gallbladder tone. The mean amplitude of gallbladder contraction in response to CCK was decreased by 45, 73, and 67% (P less than 0.01), in response to the nifedipine doses of 100, 200, and 300 micrograms, respectively. The integrated gallbladder contractile response and the rate of rise of gallbladder pressure in response to CCK were also significantly decreased by nifedipine. In nine healthy human volunteers, gallbladder emptying was measured by radionuclide cholescintigraphy in response to CCK infusion; on another day the study was repeated after oral administration of 10 mg nifedipine. Ejection fraction was significantly decreased by nifedipine from 72 +/- 5 to 51 +/- 5% (P less than 0.001). These data demonstrate that nifedipine is a potent inhibitor of gallbladder contractility in guinea pigs and man. This may provide the basis for the use of nifedipine clinically in the treatment of biliary colic and also raises questions about the potential effect of long-term nifedipine use on gallstone formation and cholecystitis.

Progesterone receptors regulate gallbladder motility.

The increased incidence of gallstones in multiparous women may be related to hormonal effects on the gallbladder and its contractility. The occurrence of estrogen and progesterone receptors were studied in the gallbladders of three groups of female guinea pigs (normals, oophorectomized, and oophorectomized treated with estrogen + progesterone for 14 days). Gallbladder contractile response in vivo to cholecystokinin (CCK) was related to the presence of these receptors. The gallbladders from normal females showed low progesterone and estrogen binding activity (4.9 +/- 2.0 and 2.4 +/- 0.8 fmoles/mg cytosol protein). Oophorectomized females had no detectable progesterone or estrogen receptors, but after treating oophorectomized females for 14 days with estrogen + progesterone, gallbladder concentrations of progesterone receptors increased significantly to 14.7 +/- 5.9 fmoles/mg and estrogen binding activity was minimally detectable at 1.4 +/- 0.8 fmoles/mg. The gallbladder contractile response to CCK was inversely related to the concentration of progesterone receptors in the gallbladder wall. These data suggest that the gallbladder contains progesterone receptors which are susceptible to circulating hormonal conditions and which have a regulatory effect on gallbladder contractility.