Summary
The purpose of this study was to define better the influence of hormones on the normal and pathological development of the anterior pituitary using Rathke's pouch (RP)-derived model system. RP from either 12- or 15-day fetuses were microsurgically isolated and transplanted beneath the kidney capsule (KC) of intact adult hosts. Eighteen days later the hosts were hypophysectomized. Ten-12 days after hypophysectomy hosts were injected daily with either 1.0 μg estradiol benzoate (EB) or 0.1 cc corn oil until necropsy at 80 days. Both 12- and 15-day RP differentiated into large, pars distalis tissues consisting of a variety of granulated and agranulated cell types, as well as large, secretory cysts. Cytodifferentiation was consistently most advanced in 15-day RP-derived grafts. Evidence of secretory granule synthesis, but not exocytosis, was apparent in granulated cells in oil-treated controls and EB-treated 12-day RP-derived grafts. Immunostaining and electron microscopy demonstrated hypertrophied somatotrophs and mammotrophs with numerous profiles of exocytosis in EB-treated 15-day RP-derived grafts. Mammotrophs and somatotrophs were infrequent and not well differentiated in 12-day RP-derived grafts whether EB- or oil-treated, nor in oil-treated 15-day RP-derived grafts. Radioimmunoassay demonstrated highest levels of plasma PRL in EB-treated 15-day RP-derived grafts. Implant invasiveness was noted only in EB-treated 12-day RP-derived grafts when basal laminae were disrupted or absent, and graft cells mixed with connective tissue elements.
Results indicate that the Cytodifferentiation of pars distalis cell types derived from KC transplanted RP can be maintained to 80 days. Mammotrophs are especially well differentiated and responsive to EB treatment during this development. However, continued maintenance of a differentiated state by mammotrophs and somatotrophs appears to require the presence of host pituitary and/or end organ hormones as evidenced by the lack of maintenance in oil-treated controls. Furthermore, the loss of well defined tissue boundaries between host and graft tissues of EB-treated 12 day RP animals suggests tumorigenic transformation.
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Supported in part by Grant No. R01-CA-21426 from the National Cancer Institute, DHEW; California Division ACS Special Grant No. 851; HEW-NIH Grant CA-14089, Los Angeles County/USC Cancer Center; and GRS 53-5104-5283
The authors gratefully acknowledge the technical assistance of Vivian Valentin, Alicia Thompson, Linda Melsek, Carolyn Tallent, and Lindsay Gilpin.
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Schechter, J., Gash, D. & Ahmad, N. Estradiol stimulation of pituitary primordia transplanted to the kidney capsule. Cell Tissue Res. 227, 41–53 (1982). https://doi.org/10.1007/BF00206330
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DOI: https://doi.org/10.1007/BF00206330