Bee Venom Stimulates Hormone Secretion in Rat Somatotroph and Corticotroph Cells: Digital Image Analysis of Secretory Granules.

In this study, we characterized secretory granules in somatotroph (STCs) and corticotroph (CTCs) cells from the anterior pituitary of rats, in conjunction with different experimental treatments with bee venom (BV). In the rats injected for 30 days with daily BV doses equivalent to one sting, we found significant changes in secretory granules' diameter: reduced by 48.15% in STCs and increased by 5.09% in CTCs, and especially a shift to gray into their intensity profile: increased by 237.04% in STCs and by 212.38% in CTCs. In the rats injected with a single high BV dose, the granules' diameter was reduced in both STCs (by 7.14%) and CTCs (by 4.67%-significant) and their gray intensity profile increased by 200% in STCs and by 51.71% in CTCs (both are significant). The changes in the gray profile reflected a reduced content of granules in the cells, consistent with an increase of the plasma levels of GH and ACTH in all cases. We concluded that the reduced hormone cargo of granules in STCs and CTCs resulted from an accelerated cell secretion. The results obtained for the two types of cells correlated, indicating a similar reaction of these secretory cells to the prolonged and acute presence of BV in the organism.

Arginine vasopressin (AVP): a review of its historical perspectives, current research and multifunctional role in the hypothalamo-hypophysial system.

INTRODUCTION: This publication reviews the function of arginine vasopressin and focuses on the morphologic and functional correlation between the hormone and its effect on stress, the hypophysial-adrenocortical axis, neuroimmune responses, renal function and corticotroph pituitary tumors. MATERIALS AND METHODS: A literature review was performed using various search engines for information regarding the morphology and the multifunctional role of arginine vasopressin. RESULTS: Although a large number of studies were published discussing these interactions, there are several important areas that are still obscure. CONCLUSION: The questions of how does arginine vasopressin affect the morphology and function of these various areas, and how does the secretion of ACTH and adrenocortical hormones influence the morphology of arginine vasopressin-producing cells and their hormone secretion requires further investigation.

Clinical Parameters to Distinguish Silent Corticotroph Adenomas from Other Nonfunctioning Pituitary Adenomas.

BACKGROUND: It is difficult to distinguish silent corticotroph adenomas (SCAs) from other nonfunctioning pituitary adenomas (NFPAs) preoperatively. This study aimed to determine the preoperative clinical parameters associated with SCAs. METHODS: This was a retrospective single-center study of patients who underwent surgery for NFPAs during 2011-2016 in our tertiary hospital and who had preoperative combined pituitary function test (CPFT) and immunohistochemical staining results available. After we excluded patients with increased 24-hour urinary free cortisol to preclude overt Cushing's disease, 341 patients were finally enrolled. The medical records, including the CPFT and immunohistochemistry results, of the patients were reviewed. RESULTS: The age and tumor size were similar between patients with SCAs and other NFPAs. The SCA group had a greater proportion of women (89.2% vs. 57.6%, P < 0.001), cavernous sinus invasion (35.1% vs. 20.7%, P = 0.047), and intratumoral hemorrhage on preoperative sella magnetic resonance imaging (32.4% vs. 9.2%, P < 0.001) compared with the NFPA group. In the preoperative CPFT, the cortisol response was not significantly different between groups. However, the peak adrenocorticotropic hormone (ACTH) (67.80 ± 49.83 vs. 85.67 ± 78.97 pg/mL, P = 0.061) tended to be lower, and the ΔACTH (53.71 ± 50.14 vs. 72.67 ± 75.82 pg/mL, P = 0.046) was significantly lower in SCAs. After we excluded patients with preoperative hypopituitarism caused by mass effects, the peak ACTH (69.39 ± 39.45 vs. 119.75 ± 89.84 pg/mL, P = 0.001) and ΔACTH (58.58 ± 36.51 vs. 107.66 ± 86.05 pg/mL, P = 0.001) were significantly lower in SCAs than in other NFPAs. CONCLUSIONS: Female sex, cavernous sinus invasion, intratumoral hemorrhage on sella magnetic resonance imaging, and decreased ACTH response in the CPFT are independent indicators of SCAs.

Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

Adiponectin regulates ACTH secretion and the HPAA in an AMPK-dependent manner in pituitary corticotroph cells.

It is known that adipokines can regulate the hypothalamic-pituitary-adrenal axis (HPAA). In this study, we confirmed that adiponectin regulates the HPAA by affecting pituitary corticotroph cells. Using RT-PCR and immunofluorescence, we determined that adiponectin receptors were expressed in pituitary corticotroph tumour cells (AtT-20 cells and human corticotroph tumours). Adiponectin stimulated calcium influx and increased basal ACTH secretion without affecting corticotrophin-releasing hormone (CRH)-stimulated ACTH secretion, which was most likely due to the expression of adiponectin repressing CRH receptor 1 (CRHR1). Adiponectin also acutely stimulated ACTH release in primary culture pituitary cells. Lastly, adiponectin directly phosphorylated 5' AMP-activated protein kinase (AMPK) in AtT-20 cells. The effects of adiponectin were mimicked by AICAR, which was blocked by compound C. Taken together, our results suggested that adiponectin stimulated ACTH secretion and down-regulated CRHR1, possibly via an AMPK-dependent mechanism in pituitary corticotroph cells.

Symptomatic cystic degeneration of a clinically silent corticotroph tumor of the pituitary gland.

Clinically silent corticotroph tumors of the pituitary gland are those tumors that stain for adrenocorticotropic hormone (ACTH) but do not manifest with clinical or laboratory features of Cushing disease. These tumors have been described as exhibiting more aggressive behavior than other nonfunctional pituitary tumors. We present an unusual case of a clinically silent corticotropic adenoma of the pituitary gland that underwent cystic degeneration following recurrence after transsphenoidal surgery and radiation therapy. The patient underwent left frontotemporal craniotomy with resection of the suprasellar mass and decompression of the left optic nerve. Postoperative magnetic resonance imaging demonstrated no further optic chiasm or nerve compression. Patients with clinically silent ACTH-secreting tumors should be monitored for aggressive tumor behavior and may require closer follow-up than those patients harboring other nonfunctional tumors.