Sex-Steroid Enzymes, Aromatase and 5α-Reductase in the Pancreas: A Comparison of Normal Adult, Foetal and Malignant Tissue

Abstract

1. Following the finding of high levels of oestrogen receptor proteins in pancreatic carcinoma tissue, two enzymes involved in sex-steroid biosynthetic pathways, aromatase and 5 alpha-reductase, have been measured. 2. Activities of aromatase, which converts testosterone into oestradiol, comparable with those found in pre-menopausal uterus (P less than 0.5) were found in all seven samples of pancreatic carcinoma tissue, and in a pooled sample of foetal pancreas. Measurable but significantly lower activities (P less than 0.001) of aromatase were found in seven specimens of normal pancreas. 3. 5 alpha-Reductase activity, which converts testosterone into the more potent androgen 5 alpha-dihydrotestosterone, was found in malignant pancreatic tissue at approximately half the level found in prostatic tissue (P less than 0.01) and at almost twice the levels found in either normal adult or pooled foetal pancreatic tissue (P less than 0.01). 4. These findings suggest that sex steroids are involved in foetal and adult pancreatic physiology. 5. Since these enzyme pathways are present in pancreatic carcinoma at greater levels than those in normal adult pancreas, it is possible that agents known to interfere with steroid metabolism could be of value in the treatment of this tumour.

Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones.

“…Somatostatin has been shown to suppress exocrine pancreatic secretion in rats, dogs and humans (11,12,14,18 (34) and found that testosterone levels were significantly reduced in patients with pancreatic carcinoma when compared to controls, possibly due to the uptake and metabolism within the tumor (34,35). The findings that pancreatic adenocarcinomas might be sex steroid dependent are supported by evidence from xenografts of human pancreatic adenocarcinomas in nude mice (36).…”

Effects of aminoglutethimide, alone and in combination with surgical castration, on pancreatic carcinogenesis in rats and hamsters

“…Moreover, in comparison with patients showing gastrointestinal tumours other than those of the pancreas and patients without malignancies, pancreatic-cancer patients exhibited significantly lower testosterone serum levels, which have been ascribed to interaction of testosterone with specific receptors on pancreatic-tumour cells (Fernandez del Castillo et af., 1990). Furthermore, significantly higher activity of aromatase and Sa-reductase have been found in pancreatic turnours in comparison with normal pancreas (Iqbal et al, 1983).…”

LH – RH Analogue Treatment in Adenocarcinoma of the Pancreas: A Phase II Study

“…The average survival is 6 months with an overall 5-year survival rate of less than 1% [2], Most of the reports evaluating treatment with cytotoxic drugs and/or radiation did not show any improvement in survival [3], Following the sug gestion by Greenway et al [4], a series of reports [5][6][7][8] have investigated estrogen receptor activity, estradiol binding proteins and growth response to estrogens and anti estrogens in different pancreatic cell lines. In 1983,Iqbalet al [9] found sex-steroid biosynthetic enzymes (aromatase and reductase) in pancreatic cancer tissue, while, in 1986, Corbishley et al [10] demonstrated androgen receptors in pancreatic cells, including human cancer cells. More re cently, a derangement in the serum androgen profile has been reported [11,12] with the suggestion that the testos terone concentration is significantly lower in patients with pancreatic cancer, while the level of androstenedione is higher, due to an increased uptake and metabolism by the tumourcells.…”