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Author’s Response: The Role of Human Chorionic Gonadotropin and cAMP/Protein Kinase A Signaling in the Differentiation of Human Endometrial Stromal Cells

Department of Obstetrics and Gynecology Shiga University of Medical Science Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan

Address all correspondence to: Kenji Takakura, M.D., Ph.D., Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.

To the editor:

Dr. Rao may have misread or misinterpreted the section in our paper about the specimens used in the study. As described in Materials and Methods and Results, we have used not only the mid-to-late luteal phase specimens but also the follicular phase and periovulatory phase specimens, and we have observed the same results in experiments using these specimens derived from the various stages of the menstrual cycle.

The purpose of our study was not only to reconfirm the presence of LH/CG receptor in in vitro decidualized human endometrial stromal cells but also to explore the existence of the functional receptor, which can (cross)-react with purified human (h) CG.

Several investigators in other laboratories, including Dr. T. Inoue et al. in Kyoto University (in personal communication), also agreed with our findings that hCG never directly induces or promotes in vitro decidualization of human endometrial stromal cells in terms of morphological transformation and PRL secretion. Moreover, we have also obtained the same results as Stewart et al. (1). We agree with Dr. Rao’s understanding on Ref.1 , which postulated the presence of a variant or unique hCG receptor in the human endometrium. However, according to the results of our repeated experiments, we believe the possibility that the functional LH/CG receptor is not present in in vitro decidualized human endometrial stromal cells.

Concerning the bioactivity of hCG used in the study, we have also verified it by another experiments described in our Refs. 2, 3, 4, 5, 6 , using porcine and human granulosa cells.

Concerning cAMP signaling, our observation is in agreement with that reported by Telgmann et al. (7) on per well data (Fig. 7A in our paper). As we described in Results and Discussion, when our data are interpreted by per cell evaluation, protein kinase inhibitor failed to suppress estradiol/P-induced PRL secretion.

We agree that it should be prudent to interpret the experimental results using human in vitro decidualized endometrial stromal cells, because they are heterogeneous and it has been reported that at least two cell types are included, PRL-producing and -nonproducing cells. We do not know much about the differences among those types of the cells, and we do believe that the presence of functional LH/CG receptors and direct actions of hCG on human endometrium are still a controversial issue.

Received April 26, 2001.

References

1. Stewart EA, Sahakian M, Rhoades A, Van Voorhis BJ, Nowak RA 1999 Messenger ribonucleic acid for the gonadal luteinizing hormone/human chorionic gonadotropin receptor is not present in human endometrium. Fertil Steril 71:368–372[CrossRef][Medline]
2. Fukuoka M, Yasuda K, Taii S, Takakura K, Mori T 1989 Interleukin-1 stimulates growth and inhibits progesterone secretion in cultures of porcine granulosa cells. Endocrinology 124:884–890[Abstract/Free Full Text]
3. Fukuoka M, Taii S, Yasuda K, Takakura K, Takahide Mori T 1989 Inhibitory effects of interleukin-1 on luteinizing hormone-stimulated adenosine 3',5'-monophosphate accumulation by cultured porcine granulosa cells. Endocrinology 125:136–143[Abstract/Free Full Text]
4. Yasuda K, Fukuoka M, Taii S, Takakura K, Mori T 1990 Inhibitory effects of interleukin-1 on follicle-stimulating hormone induction of aromatase activity, progesterone secretion and functional luteinizing hormone receptors in cultures of porcine granulosa cells. Biol Reprod 43:905–912[Abstract]
5. Iwai M, Yasuda K, Fukuoka M, et al. 1991 Luteinizing hormone induces progesterone receptor gene expression in cultured porcine granulosa cells. Endocrinology 129:1621–1627[Abstract/Free Full Text]
6. Fukuoka M, Yasuda K, Emi N, et al. 1992 Cytokine modulation of progesterone and estradiol secretion in cultures of luteinized human granulosa cells. J Clin Endocrinol Metab 75:254–258[Abstract]
7. Telgmann R, Maronde E, Tasken K, Gellersen B 1997 Activated proteim kimase A is required for differentiation-dependent transcription of the decidual prolactin gene in human endometrial stromal cells. Endocrinology 138:929–937[Abstract/Free Full Text]

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