自体吞噬与类固醇激素分泌调节的关系

本实验用腹腔内给予下丘脑激素或类固醇激素的方法，造成大鼠睾丸间质细胞和肾上腺皮质束状带细胞处于分泌兴奋或抑制状态，对这两种分泌类固醇激素细胞中的溶酶体和自噬小体进行了超微结构、细胞化学和形态计量研究。结果表明，在类固醇激素分泌增多时，细胞中自体吞噬活动减弱；激素分泌减少时，自体吞噬活动加强。这一结果证明了细胞内的自体吞噬活动与类固醇激素的分泌调节有密切关系，自体吞噬是溶酶体参与激素分泌调节过程的一种重要方式。     

Lysosomes in normal pancreatic beta cells

Summary Lysosomes and their relationships with surrounding organelles were studied in pancreatic B-cells of normal Wistar rats by electron microscopy and cytochemical localization of acid phosphatase (AcPase) and arylsulphatase. Several forms of lysosomes were distinguished and shown to interact frequently with the secretory granules. Two different digestive processes were recognized. During crinophagy, lysosomes directly fuse with secretory granules while, during autophagy, a cytoplasmic area containing secretory granules and/or other organelles is circumscribed before the enzymatic digestion. In addition, lysosomes may transport arylsulphatase into secretory granules apparently not involved in a destructive process. Such a process could also account, at least in part, for the presence of AcPase in a certain number of mature and immature secretory granules.     

Crinophagy in Thyroid Follicular and Parafollicular Cells of Male Obese Zucker Rat

Comparison between lean (Fa/?) and obese (fa/fa) young adult male Zucker rat thyroids reveals that obese rats display larger clusters of parafollicular cells than the lean ones with a lesser blood supply. Fa/? thyroid typically shows single or “twin” C cells in follicles; fa/fa parafollicular cells appear with three functional aspects. Crinophagy is found in the fa/fa C cells amassing numerous aberrant calcitonin-containing vesicles among which lysosomes build these autophagic bodies by capturing vesicle contents, other organelles and, fusing with each other, increase their size. Other C cells contain many secretory vesicles but show few or no crinophagic structures. Another parafollicular cell type is revealed with scant organelles and highly contrasted secretory vesicles, different from calcitonin. Hypercalcemia of fa/fa rats corresponds to increased C cells population with accrued calcitonin production but a low calcitonin plasma level – verified by others – is likely caused by crinophagy of the altered vesicles. In addition, the T thyrocytes of fa/fa rats exhibit crinophagy bodies; this can confirm their hypothyroidism. Possibly, the known leptin mutation along with other unknown paracrine secretions alter both T and C thyrocytes’ functions of the fa/fa rats, allowing high intracellular calcium and lower pH favoring autophagocytosis. Other longitudinal, interdisciplinary studies should further clarify the complex paracrine interactions existing between these endocrine structures because this animal model could be useful to understand human defects, such as the metabolic syndrome that involves obesity, cardiovascular, renal, hepatic, non-insulin dependent diabetes mellitus (NIDDM), hypothyroidism defects, as well as the etiology of thyroid medullary tumors.     

Crinophagy in Neuroblastoma: A Case Report and Review of the Literature

Abstract

Crinophagy is a well-described ultraphysiological phenomenon encountered in a variety of cells and tissues. This process reflects a form of autophagy in which degradation of excess or nonfunctional cellular constituents occurs, specifically of neuroendocrine granules. The diagnostic ultrastructural features are the identification of neuroendocrine granules within lysosomes, often encased in or accompanied by myelin bodies. An impressive variety of neuroendocrine/secretory cells and tumors have demonstrated crinophagy from the neuroendocrine cells of the pancreas, small bowel, prostate, and urinary tract. To our knowledge, however, crinophagy has not been previously described in neuroblastoma, despite the fact that these tumors characteristically produce neuroendocrine granules in abundance. This case further supports the idea that crinophagy represents a common ultrastructural mechanism for the disposal and degradation of excess neuroendocrine granules.     

Resistance of the insulin crystal to lysosomal proteases: implications for pancreatic B-cell crinophagy

Summary Insulin is thought to be chemically stabilized within -granules in the crystal form. The other major products of the -granule, proinsulin and C-peptide, by contrast, are not thought able to crystallize. The physico-chemical properties of peptides in soluble or crystalline form are dramatically different. The ability of insulin to crystallize in the -granule might thus explain why this peptide, but not proinsulin/Cpeptide, remains stable even after its introduction into lysosomes as occurs during granulolysis (crinophagy). We have now studied this by exposing proinsulin or insulin to lysosomal proteases in vitro. ¹²⁵I-insulin in soluble form was found to be degraded at the same rate as ¹²⁵I-proinsulin. Strikingly, however, when the labelled insulin was crystallized, its rate of degradation was decreased from 1.9 to 0.2 pmol/min. We take these data as confirmation that the insulin crystal is resistant to degradation, thereby possibly accounting for (a) the presence of insulin immunoreactivity within multigranular bodies, and (b) the unusually slow rate of degradation of insulin within B cells compared with that of other hormones in their cells of origin.