Transplantation of Human Pituitary Adenomas into Nude Mice

Abstract

Invitro studies with human pituitary adenomas are limited by the small amount of tissue obtained, which may be contaminated by the surrounding normal pituitary tissue. In this study we investigated if the passage of adenoma tissue via thymusless nude mice could solve some of these problems. The secretory capacity of the transplanted human pituitary adenomas was demonstrated by the presence of hGH and/or hPRL in the plasma of the host mouse, while other human pituitary hormones (TSH, LH and FSH) were undetectable. The transplants, however, decreased in size with time although histologically viable adenoma tissue was recovered that resembled the original tumor. Upon trypsinization of the small tissue fragments no viable adenoma cells could be obtained. In contrast, an experimental malignant rat pituitary tumor grew steadily with time, resulting in high levels of rPRL in the nude mice recipients. Large numbers of viable tumor cells were recovered from these tumors. Thus, human pituitary adenomas transplanted in nude mice continue to release hormone(s), but the transplants decrease in size and cannot be used to isolate dispersed tumor cells for in vitro studies.

Use of Athymic Nude Mice for in vivo Studies of Human Growth-Hormone-Secreting Pituitary Adenomas

“…We confirm previous reports inasmuch as we did not observe macro-or microscopic signs of growth in the transplanted human pituitary adenomas [3][4][5][6][7][8][9][10], Histo logical alteration of the pituitary adenomas after trans plantation was never detected [7,8,10], According to four publications, blood was drawn at the end of the experiments and examined for plasma hGH levels [7,8,12,15]. These data correspond to ours.…”

“…Transplantation experiments of hGH-secreting pitu itary adenomas on nude mice were so far performed on a small scale [3][4][5][6][7][8][9][10][12][13][14], With one exception [12] only a maintenance of vitality on the new host was achieved. Different methods of transplantation were investigated supposing that the lack of growth of the transplants might depend on the absence of stimulating hypotha lamic hormones [5,13,14].…”

“…Xenotransplants of many malig nant tumors grow very well in the nude mouse host [2], Growth of human pituitary adenoma xenograft on nude mice was reported to be poor. However, due to the low rate of vital transplant maintenance, xenografting of pituitary adenomas on athymic nude mice has turned out to be unreliable, and experience with this method is limited [3][4][5][6][7][8][9][10]. Performing morphological and endocri nologie studies in a large series of cases, we looked for new methods to overcome this disadvantage and to give the opportunity of reliable in vivo research with these tumors.…”

Effects of suramin on hormone release by cultured rat anterior pituitary cells

“…The anterior pituitary lobes were dissociated with dispase, a neutral protease from Bacillus polymyxa (grade II, final concentration 2.4 X lo3 U/l; Boehringer Mannheim, Mannheim, F.R.G.) as described in detail previously (Oosterom et al, 1983a). Viability of the cells, as determined by trypan blue exclusion, was greater than 90%.…”

“…The studies on ACTH release were carried out after 2 days of culture, since this was previously shown to be the most suitable time of measuring optimal ACTH release by cultured pituitary cells (Lamberts et al, 1986). The studies on prolactin (PRL), growth hormone (GH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release were carried out between days 4 and 7 (Oosterom et al, 1983a;Grootenhuis et al, 1989). The media were refreshed prior to incubation times which were 3 h in the studies on ACTH release, 4 h in the studies on PRL and GH release and 6 or 72 h in the studies on LH and FSH release.…”