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Feedback effects of mammary gland tumors on the host pituitary prolactin cell
Abstract:
Prolactin (PRL) cells in pituitary glands of F-344 female rats bearing transplantable mammary gland adenocarcinomas (13762, 3230) were smaller, contained less intracellular hormone, and released less hormone in culture relative to non tumor-bearing littermates. In some instances removal of the tumor by surgery or chemotherapy (PAM) resulted in restoration of function in vitro. On the other hand, PRL cells from pituitaries of breast cancer patients were often hypertrophied. Since these patients had mastectomies prior to hypophysectomy, the data are consistent with the hypothesis that the tumor exerts negative feedback at the pituitary or hypothalamic level. In support of this hypothesis we have discovered a potent PIF in rat serum. In addition, an experimental protocol involving a) encapsulation of pituitary cells in Amicon hollow fibers, b) their implantation in ectopic sites and c) their subsequent in vitro culture yields data which suggest that the brain of the tumor bearing rat suppresses PRL release. It is suggested that decreased PRL cell function in animals bearing certain mammary tumors ultimately favors metastatic activity of the tumor cell.
Insights
Mammary tumors in rats decrease prolactin (PRL) cell function, potentially favoring metastasis. Tumor removal can restore PRL cell function, suggesting a feedback mechanism.
Area of Science:
- Endocrinology
- Oncology
- Neuroendocrinology
Background:
- Prolactin (PRL) plays a role in mammary gland function and tumor development.
- The relationship between mammary tumors and pituitary PRL cell function is not fully understood.
Purpose of the Study:
- To investigate the effect of mammary tumors on pituitary PRL cell function in rats and breast cancer patients.
- To explore the potential feedback mechanisms involved in PRL regulation during tumorigenesis.
Main Methods:
- Comparison of PRL cell size, intracellular hormone content, and in vitro hormone release between tumor-bearing and non-tumor-bearing rats.
- Assessment of PRL cell function after tumor removal (surgery or chemotherapy).
- Examination of PRL cells from breast cancer patients.
- Detection of a prolactin-inhibiting factor (PIF) in rat serum.
- Ectopic implantation of encapsulated pituitary cells in tumor-bearing rats to assess brain-mediated suppression of PRL release.
Main Results:
- Pituitary PRL cells in tumor-bearing rats were smaller and released less PRL compared to controls.
- Tumor removal or chemotherapy partially restored PRL cell function in rats.
- PRL cells from breast cancer patients often showed hypertrophy.
- A potent PIF was identified in rat serum.
- Ectopic pituitary cell implantation suggested brain suppression of PRL release in tumor-bearing rats.
Conclusions:
- Mammary tumors may exert negative feedback on the pituitary or hypothalamus, suppressing PRL release.
- Decreased PRL cell function in the presence of certain mammary tumors might promote tumor cell metastatic activity.
- The findings suggest a complex interplay between mammary tumors, PRL regulation, and tumor progression.