Hypothalamic-Pituitary autoimmunity and related impairment of hormone secretions in chronic fatigue syndrome

Context Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe chronic illness which reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. Objective To investigate the occurrence of anti-pituitary (APA) and anti-hypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. Design, Setting, Patients and Other Participants This is a case-control study conducted in University Hospital setting (Stanford, Naples). Thirty women with ME/CSF (Group 1) diagnosed according to Fukuda, Canadian, and IOM criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. Main Outcome Measures APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands and plasma and urinary osmolality. Both APA and AHA titers were assessed and the prevalence of pituitary hormone deficiencies was also investigated. Results Patients in Group 1 showed a high prevalence of AHA (33%) and APA (56%) and a significant lower levels of ACTH/cortisol, and GH peak/IGF1 vs controls (all AHA/APA negative). Patients in Group 1A (13 patients positive at high titers, ≥1:32) showed ACTH/cortisol and GH peak/ IGF1 levels significantly lower and more severe forms of ME/CFS with respect to patients in Group 1B (7 positive at middle/low titers,1:16-1:8) and 1C (10 Ab negative patients). Conclusions Both AHA and/or APA at high titers associated with hypothalamic/pituitary dysfunction suggest that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d’étude des Tumeurs Endocrines) Study

Aim To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs). Background The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense. Methods Thirty-one MEN1 patients from the Groupe d’étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed. Results Indication for surgery was: Zollinger–Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0–433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13–110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8–98.3] and ten-year overall survival was 89.1% [CI 69.6–96.4]. After a mean follow-up of 151 months (range 0–433), the biochemical cure rate for MEN-1 related gastrinomas was 61%. Conclusion In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.

High-quality genome assembly of Metaphire vulgaris

Earthworms enrich the soil and protect the health of their ecological environment. Previous studies on these invertebrates determined their protein content, hormone secretions, medicinal value, and ecological habits, but their whole genomic sequence remains incomplete. We performed whole genome sequencing of Metaphire vulgaris (Chen, 1930), which belongs to the genus Metaphire of the family Megascolecidae. The genome assembly was 729 Mb, with a N50 contig size of 4.2 Mb. In total, 559 contigs were anchored to 41 chromosomes according to the results of Hi-C (High-throughput Chromosome Conformation Capture) technology, which was confirmed by karyological analysis. A comparison of the genomic sequences and genes indicated that there was a whole-genome duplication in M. vulgaris followed by several chromosome fusion events. Hox genes and lumbrokinase genes were identified as partial clusters surrounding the genome. Our high-quality genome assembly of M. vulgaris will provide valuable information for gene function and evolutionary studies in earthworms.

Effects of neuromedin B on steroidogenesis, cell proliferation and apoptosis in porcine Leydig cells

Neuromedin B (NMB), a mammalian bombesin-related peptide, has numerous physiological functions, including regulating hormone secretions, cell growth, and reproduction, by binding to its receptor (NMBR). In this study, we investigated the effects of NMB on testosterone secretion, steroidogenesis, cell proliferation, and apoptosis in cultured primary porcine Leydig cells. NMBR was mainly expressed in the Leydig cells of porcine testes, and a specific dose of NMB significantly promoted the secretion of testosterone in the primary Leydig cells; moreover, NMB increased the expression of mRNA and/or proteins of NMBR and steroidogenic mediators (steroidogenic acute regulatory (STAR), CYP11A1, and HSD3B1) in the Leydig cells. In addition, specific doses of NMB promoted the proliferation of Leydig cells and increased the expression of proliferating cell nuclear antigen and Cyclin B1 proteins, while suppressing Leydig cell apoptosis and decreasing BAX and Caspase-3 protein expression. These results suggest that the NMB/NMBR system might play an important role in regulating boar reproductive function by modulating steroidogenesis and/or cell growth in porcine Leydig cells.

Effects of methyl-beta-cyclodextrin on the release of luteiniz-ing hormone, follicle stimulating hormone, prolactin and growth hormone from cultured bovine anterior pituitary cells

The aims of the present study are to clarify the effect of methyl-beta-cyclo-dextrin (MβCD) on the secretions of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and growth hormone (GH) from the anterior pituitary (AP) cells of prepubertal male cattle and to compare the characteristics of secretion to those of gonadotrophic-releasing hormone (GnRH), thyrotropin- releasing hormone (TRH) and growth hormone-releasing hormone (GHRH), respectively. The AP cells prepared from six castrated Holstein calves (age: 8-11 months) were incubated for 2 h with MβCD (10-3 M, 10-2 M), GnRH (10-8 M), TRH (10-8 M) and GHRH (10-8 M) or vehicle only as a control (CTL). The amount of LH, PRL and GH released in the medium was measured by a time-resolved fluoroimmunoassay (TRFIA). The amount of FSH released in the medium was measured by the radioimmunoassay (RIA). MβCD significantly (P<0.05) stimulated the secretion of LH, FSH, PRL and GH from the AP cells. Furthermore, GnRH significantly (P<0.05) stimulated the secretion of LH and FSH. Also, TRH and GHRH significantly (P<0.05) stimulated the secretion of PRL and GH, respectively. However, the potency of the MβCD was less compared to each respective hormone secretions in response to GnRH, TRH and GHRH (P<0.05).

Coping with the extremes: stress physiology varies between winter and summer in breeding opportunists

Seasonal changes in stress steroid hormone secretions are thought to reflect investment in self-maintenance versus reproduction. The capricious conditions hypothesis (CCH) posits that reduced corticosterone (CORT) secretion during stress coincident with parental phases of breeding is necessary in harsh environments because a full response would otherwise trigger repeated nest abandonments. To test this hypothesis, we measured seasonal changes in stress physiology in free-living red crossbills ( Loxia curvirostra ), an opportunistically breeding songbird that regularly breeds in summer and winter. This species allows unique comparisons of breeding physiology under very different seasonal environmental conditions within locations. We found strong support for the CCH: red crossbills showed reduced CORT secretion only when in high reproductive condition in the winter, when compared with summer breeders and winter non-breeders. These data demonstrate that behavioural status and local environmental conditions interact to affect mechanisms underlying investment trade-offs, presumably in a way that maximizes lifetime reproductive success.