Development of an experimental ovarian tumor: immunocytochemical analysis

Abstract

Objective: The aim of the present work was to study whether immunocytochemical parameters present in the normal ovary were altered after tumor development under high gonadotropin levels. Methods: Ovarian tumors (luteoma): castrated female rats had an ovary grafted into the spleen; tumors were left to develop for 1, 2, 3 or 7 months. The presence of apoptotic cells (TUNEL method) and the expression of proliferating cell nuclear antigen (PCNA), gap junction protein (Cx43), steroidogenic acute regulatory protein (StAR), aromatase and synaptosome-associated protein of 25 kDa (SNAP-25) were determined by immunocytochemistry. Some of these findings were confirmed by RT-PCR (Cx43, StAR, SNAP-25). Inhibin subunit mRNAs were investigated by Northern blot. Results: PCNA staining of tumors was mainly found in granulosa cells of transforming follicles and was absent from luteinized follicles. A nearly complete absence of apoptosis was observed. Cx43 was mainly found in follicles, while it was very weakly expressed or absent in luteinized follicles. StAR protein expression, indicating active steroidogenesis, was demonstrated only in luteinized follicles and in thecal cells, but was absent from granulosa cells. Aromatase immunoreactivity was very intense in granulosa and also present in luteal cells. Membrane-associated and cytoplasmic SNAP-25 immunostaining was determined in patches of endocrine cells in the follicles, as well as in the luteinized follicles. The expression of mRNAs for Cx43, StAR and SNAP-25 (RT-PCR) and inhibin subunits (Northern blots) were confirmed in 1-, 3-and 7-month-old tumors. Conclusions: These results indicated that luteoma most likely develop from unruptured follicles by hypertrophy and proliferation of follicular cells. Circulating gonadotropins seem to play a fundamental role in maintaining the expression of proteins typically expressed in normal ovary, while avoiding apoptosis in this tissue.

Actions of Immunosuppressor Drugs on the Development of an Experimental Ovarian Tumor1

“…The histological analysis showed that 86% of the tumors presented highly luteinized tissue, whereas II % showed granulosa cell predominance (Table II). No signs of corpora lutea involution were observed, in agreement with lack of TUNEL-positive cell detection in these tumors (30). Immunosuppressor treatments did not alter tumor histology, and no signs of malign transformation were observed.…”

Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays

“…The genes overexpressed in 'ovarian-type' stroma included sex hormone-related genes such as STAR and ESR1. The STAR protein, by enhancing the metabolism of cholesterol into pregnenolone, has a key role in steroid hormone synthesis, and is responsible for the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone (Sorianello et al, 2002). In the normal ovary, STAR is expressed in luteinized follicles and in theca cells (Sorianello et al, 2002).…”

“…The STAR protein, by enhancing the metabolism of cholesterol into pregnenolone, has a key role in steroid hormone synthesis, and is responsible for the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone (Sorianello et al, 2002). In the normal ovary, STAR is expressed in luteinized follicles and in theca cells (Sorianello et al, 2002). We observed overexpression of STAR transcript in 'ovarian-type' stroma, although other genes involved in progesterone and androgen biosynthesis were expressed at low levels.…”

Mucinous cystic neoplasms of the pancreas: pathology and molecular genetics

“…According to the oligonucleotide microarray analysis on MCN, the over‐expression of several genes involved in estrogen metabolism, including steroidogenic acute regulatory (STAR) protein and estrogen receptor 1 (ESR1) genes , was observed in the ovarian‐type stroma (Table 1). The STAR protein, by enhancing the metabolism of cholesterol into pregnenolone, has a key role in steroid hormone synthesis, and is responsible for the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane, where it is cleaved to pregnenolone . In the normal ovary, STAR is expressed in luteinized follicles and in theca cells.…”

“…9 The STAR protein, by enhancing the metabolism of cholesterol into pregnenolone, has a key role in steroid hormone synthesis, and is responsible for the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane, where it is cleaved to pregnenolone. 20 In the normal ovary, STAR is expressed in luteinized follicles and in theca cells. Ishiguro et al 21 found the expression of two steroidogenic enzymes, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 17 alpha-hydroxylase (17 alpha H) in the ovarian-type stroma of pancreatic MCNs.…”