The aim of this study was to characterize corpus luteum vascularization and its association with plasma progesterone concentration in early stages of pregnancy, when maternal recognition of pregnancy is expected to occur. In all animals, both plasma progesterone concentration and corpus luteum vascularization increased from Day 6 to Day 8 post‐mating and afterwards in non‐pregnant llamas they started to decrease to reach basal levels around Days 12 to 14 post‐mating, while in pregnant animals, both variables remained elevated until the end of the study. A lineal positive relationship between corpus luteum vascularization and plasma progesterone concentration was observed in pregnant (r2 = .46, p < .0001) and non‐pregnant llamas (r2 = .66, p < .0001). Pregnant animals showed higher plasma progesterone concentration and corpus luteum vascularization than the non‐pregnant ones from Day 12 post‐mating until the end of the study (p ˂ .05 and p ˂ .01, respectively). These results suggest that maternal recognition of pregnancy should occur before Day 12 post‐mating in order to expand luteal lifespan, maintaining corpus luteum vascularization and progesterone production. Also, the assessment of CL vascularization area could be a useful and non‐invasive method for early pregnancy diagnosis due to its association with plasma progesterone concentration.
Ectopic ACTH secretion is provoked by extra-pituitary tumours that secrete ACTH, constituting an infrequent type of Cushing Syndrome in the dog. Neuroendocrine tumours (NET) are characterised by the synthesis of peptides with hormone activity. A dog with clinical diagnosis of Cushing's syndrome and presenting an abdominal tumour located in the area of the left adrenal gland was sent to the hospital. Cortisol was not inhibited at four and eight hours after the application of low-dose dexamethasone and the cortisol/creatinine ratio was elevated (93 × 10 -6 , reference values < 10 × 10 -6 ). Plasma ACTH measurements were high (28.6 pmol/l, reference values 5.5-14.3 pmol/l). On computed tomography, the tumour was found in the meso-epigastrium, with both adrenal glands hyperplasic and no alteration of the pituitary image. The tumour was located between the two layers of the meso-colon and was removed using laparoscopy. After surgery, ACTH concentrations became normal and clinical signs remitted. The histopathological diagnosis was NET, with positive ACTH immunostaining.
SOM230 (pasireotide) is a multiligand somatostatin (SRIF) analog able to bind to somatostatin receptor (SSTR) subtypes 1, 2, 3 and 5, and trigger antisecretory and antiproliferative signaling cascades. Canines have become in vivo models to test the pharmacological treatment of corticotropinomas because they frequently develop Cushing’s disease in a spontaneous manner, due to adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Different levels of expression of SSTR2 and SSTR5 have been shown in both mouse AtT20 cells and canine tumoral corticotropinoma cells. The objective of this study was to evaluate whether SOM230 controls both tumor cell growth and hormone synthesis, therefore controlling the disease. SOM230 was tested in dogs suffering from Cushing’s disease (10 animals were treated continuously during 6 months, and another 10 were treated with 3 cycles consisting of 2 months of treatment followed by a 2-month rest period). A significant decrease in ACTH, urinary cortisol creatinine ratio, adenoma size (magnetic nuclear resonance) and improvement of clinical signs were obtained, without side effects. AtT20 cells treated with SOM230 suppressed pro-opiomelanocortin (POMC) promoter activity through SSTR2, via the Gi α-subunit, and reduced Nur77/Nurr1 transcriptional activity. We conclude that SOM230, in addition to its well-described antisecretory effects, inhibits, as shown in AtT20 cells, ACTH synthesis at the POMC transcriptional level, an effect mediated mainly through SSTR2, and limits tumor growth. The controlled Cushing’s disease in the dogs that received the treatment indicates that SOM230 has a potential therapeutic use in humans suffering from Cushing’s disease.
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