Prolactin secretion and dopamine receptors of the MtTW15 transplantable pituitary tumour

Abstract

The MtTW15 transplantable pituitary tumour grown in rats was tested in vitro for the ability of dopamine agonists to affect prolactin secretion and for the existence of dopamine receptors. Prolactin release from enzymatically dispersed cells and non-enzymatically treated tissue fragments of both the tumour and the anterior pituitary gland was determined in a cell perifusion column apparatus. Dopamine (0·1–5 μmol/l), bromocriptine (50 nmol/l) and the dopamine antagonist haloperidol (100 nmol/l) had no effect on prolactin release from the tumour cells. In contrast, dopamine (500 nmol/l) inhibited prolactin secretion from normal anterior pituitary cells in a parallel cell column and haloperidol blocked this inhibition. Although oestrogen treatment in vivo stimulated prolactin release in vitro when the tumour was removed and studied in the cell column, oestrogen had no effect on the inability of dopamine to modify the prolactin secretion. Growth hormone release from the tumour cells was not affected by dopamine. Although MtTW15 cells were refractory to dopaminergic inhibition of prolactin release, the dopamine receptors present in tumour homogenates were indistinguishable from the dopamine receptors previously defined in the normal anterior pituitary gland. The binding of the dopamine antagonist [3H]spiperone to the tumour was saturable (110 fmol/mg protein), of high affinity to one apparent class of sites (dissociation constant = 0·12 nmol/l), reversible and sensitive to guanine nucleotides. The pharmacology of the binding was defined in competition studies with a large number of agonists and antagonists. From the order of potency of these agents, a dopaminergic interaction was apparent. We conclude that the prolactin-secreting MtTW15 tumour cells appear to be completely unresponsive to dopamine or to the potent dopamine agonist bromocriptine, in spite of apparently normal dopamine receptors in the tumour.

Characterization of D2 Dopamine Receptors in Dopamine‐Resistant Prolactin‐Secreting Rat Pituitary Tumors 7315a and MtTW15

“…Some mixed PRL-secreting transplantable pituitary tumors such as the 7315a and the MtTW15, although containing high-affinity D2 receptors (Cronin et al, 1981(Cronin et al, , 1982, are refractory to dopaminergic inhibition of PRL release (Lamberts and MacLeod, 1979). Although no clear-cut explanation has yet been offered for such a phenomenon, recent data obtained in our laboratory suggest that it may be due to the presence in both tumors of significant and distinct receptorial anomalies .…”

“…Adult Buffalo and Wistar-Furth female rats (Harlan Sprague-Dawley, Indianapolis, IN, U.S.A.), 180 g of body weight, were inoculated subcutaneously with a mince of 73 15a and MtTW 15 tumor, respectively. These transplantable tumors have been carried in rats since the early 1960s (Cronin et al, 1981(Cronin et al, , 1982. Animals were housed under controlled conditions of light (1 2 h of light starting at 0600 h) and temperature (22°C) and fed water and rat pellets ad libitum.…”

The Inhibition of Phosphatidylinositol Turnover: A Possible Postreceptor Mechanism for the Prolactin Secretion-Inhibiting Effect of Dopamine*

“…Because these tumors have the same dopamine-binding characteristics as those of normal tissue (37,38), the tissue may have a postreceptor defect that is responsible for its lack of biological responsiveness. It was important to determine whether phospholipid turnover in pituitary tumor 7315a, which secretes large amounts of PRL and only a small amount of ACTH (39), is affected by dopamine.…”

Spontaneous Sparsely-Granulated Prolactin-Producing Pituitary Adenomas in Aging Rats

“…therefore, different from the tumors in our study. Another PRL/GH-secreting tumor line (MtT.WI5), possessing dopamine receptors and found to be refractory to the effects of BEC treatment, showed no decrease in blood PRL levels or tumor growth [7], There are several factors which complicate the assess ment of the results of this study. Not all old female LongEvans rats develop PRL-containing adenomas, and not all of those which do occur are sparsely granulated.…”

“…Several workers have reported that BEC fails to reduce circulaling PRL. lev els in rats bearing certain transplanted pituitary tumors [7,8,23] as well as PRL release from dispersed pituitary tumor cells [9]. The GH.i cell line apparently lacks dopamine re ceptors [6], and BEC does not inhibit PRL release from these cells [I I], However, it must be noted that the origin of the GH?…”