Paradoxical effect of gonadotrophin-inhibiting hormone to negatively regulate neuropeptide Y neurones in mouse arcuate nucleus.

Regulation of reproduction and energy homeostasis are linked, although our understanding of the central neural mechanisms subserving this connection is incomplete. Gonadotrophin-inhibiting hormone (GnIH) is a neuropeptide that negatively regulates reproduction and stimulates food intake. Neuropeptide Y (NPY) and products of the pro-opiomelanocortin (POMC) precursor (ß-endorphin melanocortins) are appetite regulating peptides produced in the neurones of the arcuate nucleus; these peptides also regulate reproduction. In the present study, we determined the effects of GnIH on NPY and POMC neurones. Using brain slices from mice with transgenes for fluorescent tags in the two types of neurone and patch clamp electrophysiology, a predominant inhibitory effect of GnIH was observed. GnIH (100 nM) inhibited the firing rate in POMC cells, confirming the results of previous studies and consistent with the stimulatory effect of GnIH on food intake. Paradoxically (i.e. because both GnIH and NPY stimulate food intake), GnIH also had a predominantly inhibitory effect on action potential activity in NPY cells. GnIH also inhibited the secretion of NPY and α-melanocyte-stimulating hormone secretion in incubated hypothalamic blocks. GnIH (100 ng) injected into the cerebral ventricles of mice did not increase the number of NPY cells that were positively immunostained for c-Fos. Finally, dual label immunocytochemistry showed that 20% of NPY neurones had close contacts from GnIH fibres/varicosities. In conclusion, we confirm a negative effect of GnIH on POMC cells and demonstrate a paradoxical reduction of electrophysiological and functional activity in NPY cells.

Pancreatic polypeptide in obese children before and after weight loss.

OBJECTIVE: Little is known concerning pancreatic polypeptide (PP) in weight loss and in childhood obesity. METHODS: Fasting PP, leptin and insulin concentrations were determined in 38 obese children and compared with 35 lean children of the same age, gender and pubertal stage. Furthermore, changes of PP concentrations over a 1-year period were analyzed in the obese children participating in a weight loss intervention program. RESULTS: Obese children had significantly (P<0.01) lower PP, and higher leptin and insulin levels compared to lean children. In multiple linear regression analysis, PP was significantly negatively correlated to body mass index (P<0.01), but not to leptin, insulin, age, gender and pubertal stage. Changes of PP did not significantly correlate to changes of insulin (r=0.07, P=0.343) and leptin (r=-0.02, P=0.459). The substantial weight loss in 17 children led to a significant (P<0.05) increase in PP and decrease in insulin and leptin. In the 21 children without substantial weight loss, there were no significant changes in PP, insulin and leptin. CONCLUSIONS: PP concentrations are decreased in obese children and independent of age, gender, pubertal stage, leptin and insulin. The decrease of PP in obese children normalized after weight loss. Therefore, low PP concentrations reflect the overweight status, rather than cause it.

Effect of natural "micronized" progesterone on the chorionic gonadotropin concentrations in cyst fluids of women with gross cystic breast disease.

Gross cystic breast disease (GCBD) is common in women, especially in the age range between 35 and the menopausal years. The present study examined the possible role of progesterone (Pg) in the chorionic gonadotropin (hCG) concentration in GCBD. The breast cyst fluids (BCFs) were drawn by fine needle aspiration between the sixth and the eighth day of the menstrual cycle and twenty days later. On the day of the first aspiration the patient began to take 100 mg of natural micronized Pg orally until the second aspiration. At both times blood samples were also taken. Determinations were done of both BCFs and blood sample using two fully automated chemiluminiscent enzyme immunometric assays. Pg has been demonstrated to induce a significant increment in hCG + free ss-hCG (median, range): 0.27 ng/ml, 0.12-6.24 vs. 1.92 ng/ml, 0.12-423.5; free ss-hCG: 0.11 ng/ml, 0.02-2.40 vs. 0.91 ng/ml, 0.02-58.40 in the BCFs, with no change in the circulating concentrations of the hormone. None of the sera studied presented levels of hCG + free ss-hCG or free ss-hCG above 0.5 ng/ml or 0.1 ng/ml, respectively. The occurrence of hCG or a derivative polypeptide in BCFs, when they are present in high concentrations suggests that this glycoprotein could be synthesized in situ and possibly involved in the pathogenesis of GCBD by the degree of differentiation of breast epithelial cells induced by the hormone.

Biochemical study of cyst fluid in human breast cystic disease: a review.

Gross cystic disease of the breast may sometimes indicate an increased risk of breast cancer. Biochemical analysis of the cyst fluid could suggest which cysts are associated with breast cancer risk, as well as providing insights into the pathophysiology of this condition. The Na+/K+ ratio appears to be associated with the histological classification of the cyst. Sulfoconjugated estrogens and androgens, especially DHEA-S, are often found at high levels. A number of gross cystic disease fluid proteins (GCDFPs) have been described, and several polypeptide growth factors including EGF and IGF-I are frequently found. It is hoped that biochemical analysis of these components of breast cyst fluids will shed further light on the role of gross cysts in relation to breast cancer.