GnRH receptors and GnRH endocrine effects on luteoma cells

Abstract

An ovary implanted into the spleen of an ovariectomized rat develops into a luteinized tumor, growing in response to gonadotrophins. Previously, it was shown that in vivo Buserelin, a gonadotrophin-releasing hormone (GnRH) analog, inhibited tumor growth. To determine if GnRH had a direct effect on tumor cells, the presence of GnRH receptors as well as the endocrine effects of buserelin were studied on tumoral tissue. GnRH receptors were present in luteoma in similar concentrations and dissociation constant (Kd) to control estrous ovaries. In vivo treatment with buserelin did not modify luteoma GnRH receptors. In organ incubations, luteoma secreted significantly higher estradiol and lower progesterone than estrous ovaries; addition of buserelin did not modify steroid secretion. The same difference in basal steroid secretion between luteoma cells and luteal cells superovulated prepubertal ovaries was observed in cell cultures. Although luteinizing-hormone (LH)-stimulated progesterone in both kinds of cells, buserelin significantly inhibited LH-stimulated progesterone only in luteoma cells. These results describe clear differences in basal steroid secretion between tumoral and normal tissue. Furthermore, they show that luteoma possess GnRH receptors similar to those in normal ovarian tissue, and that GnRH analogs have endocrine effects on these cells. Therefore, a direct effect of buserelin on luteoma cells can be postulated.

Development of an experimental ovarian tumor: immunocytochemical analysis

“…Its expression and regulation in rat granulosa cells has been found to be associated with follicular development and luteinization (47,48) and this enzyme is also frequently present in benign and malignant ovarian tumors (49). In luteoma, aromatase expression was very intense in granulosa cells and was also present in luteal cells, in agreement with high estradiol output by tumor cells (5). As with other factors described above, we suggest that high gonadotropins maintain aromatase expression in luteoma cells, in agreement with that which has been described in the normal ovary (50,51).…”

“…Therefore, although corpora lutea do not degenerate in this tumor (see above), they seem to lose some of the traits of active luteal tissue. In this regard, we have previously shown that luteoma cells secrete less progesterone and more estradiol than other highly luteinized cells (5).…”

“…We have demonstrated that this tumor depends on gonadotropins for its growth by treating tumorbearing rats with buserelin, a gonadotropin-releasing hormone (GnRH) agonist that downregulates LH and FSH secretion; this resulted in very significant tumor regression (3). A direct action of GnRH analogs on the tumor has also been demonstrated (5,6). In women, the risk of suffering ovarian cancer has been related to gonadotropin levels.…”

“…This experimental ovarian tumor is highly luteinized (luteoma) (4) and hormonally active since it secretes estradiol, progesterone and inhibins (4,5). Inhibins have been proposed as markers of ovarian tumors (13,14).…”

Direct effect of a gonadotropin‐releasing hormone agonist on the growth of canine mammary tumour cells

“…Iodination of tracer ([ 125 I]-Goserelin) and receptor assay were performed according to Chamson-Reig et al [1997].…”