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Latent Ability to Produce Human Chorionic Gonadotropin in Response to Dibutyryl Adenosine 3',5'- Monophosphate in the BeWo-NBC Trophoblastic Cell Line^*

Departments of Gynecology and Obstetrics and Biochemistry, Medical College of Wisconsin Milwaukee, Wisconsin 53226

Address requests for reprints to: Dr. Robert O. Hussa, Department of Gynecology and Obstetrics, Medical College of Wisconsin, 8700 West Wisconsin Avenue, Milwaukee, Wisconsin 53226.

The BeWo-NBC trophoblastic cell line secretes predominantly large forms of hCG± and has almost totally lost the ability to produce hCG² or complete hCG² under normal culture conditions (hCG:hCG±, <0.05). This secretion pattern also exists in some cell lines (HeLa, ChaGo, and EICo) of nontrophoblastic origin (Nature 268: 543, 1977; In Vitro 14: 775, 1978). Accordingly, BeWo-NBC cells were employed to test their response to butyrate, a stimulator of hCG and subunit secretion in nontrophoblastic cells, and to dbT (1 mM N⁶,O²- dibutyryl cAMP plus 1 mM theophylline), a stimulator of hCG secretion in trophoblastic cells. Butyrate had no effect on ± subunit secretion and produced only slight (1.5- to 2.5-fold) stimulation of hCG/hCG/² secretion in BeWo-NBC cells. By contrast, dbT stimulated hCG/hCG² secretion by 11, 122, and 640 times after 1, 2, and 3 days of incubation with BeWo-NBC cells compared to only 1.8-, 19-, and 70-fold stimulation of asubunit secretion. These results indicate that the ability to produce the ²-subunit of hCG (and intact hCG) is latent but capable of being expressed in BeWo-NBC cells, and that the hCG-producing system is more responsive in rate and degree than the system that produces the large ±-subunit. The present findings support the concept that the production of hCG² is under more stringent biological control than the production of hCG±. The BeWo-NBC cell line provides a useful model system for study of the regulation of trophoblastic hCG secretion.

^* This work was supported by Grant CA-23357 from the National Cancer Institute, DHEW.

Received April 17, 1979.