Skip to main content
Log in

Relationship between cellular DNA synthesis, PCNA expression and sex steroid hormone receptor status in the developing mouse ovary, uterus and oviduct

  • Original Paper
  • Published:
Histochemistry Aims and scope Submit manuscript

Abstract

The proliferative activities of the different cellular compartments of the developing mouse ovary, uterus, and oviduct were studied by radioautographic assessment of DNA synthesis with [3H]-thymidine labeling and by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). The distributions of estrogen and progesterone receptors (ER and PR) were studied by immunohistochemical staining. The values of the PCNA positive staining indices were a little higher than that of the radioautographic labeling indices. However, linear relations were shown for the two indices. The proliferative activities were high from postnatal day 1–7 and decreased from day 14 in the different cellular compartments of the ovary. The proliferative activities were high on days 1, 3 and decreased from day 7 in the uterus and oviduct. Staining of ER and PR was very weak in the surface epithelium, stroma and large follicles of the ovary. Positive staining for ER occurred from day 14 in the uterine epithelium and from day 7 in oviductal epithelium. Positive staining for PR was observed from day 1 in both the uterine and oviductal epithelium. However, the positivity of both ER and PR occurred from postnatal day 1 in the stromal cells of the uterus and oviduct. These results suggest that the appearance of the steroid receptors differ between the different cellular compartment of the reproductive organs. The proliferative activities have an inverse relation with the expression of the steroid hormone receptors in the female reproductive organs during developmental stages. Therefore, we propose that there is an autonomous proliferation mechanism in the development of the reproductive organs or that the proliferation is moderated by factors other than steroid hormones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alkhalaf M, Mahfoudi A, Propper AY, Adessi GL (1991) Addictive effect of oestrodiol-17-β and serum on synthesis of deoxyribonucleic acid in guinea-pig endometrial cells in culture. J Reprod Fertil 93:295–302

    Google Scholar 

  • Bigsby RM, Cunha GR (1985) Effects of progestin and glucocorticoids on deoxyribonucleic acid synthesis in the uterus of the neonatal mouse. Endocrinology 117:2520–2526

    Google Scholar 

  • Bigsby RM, Cunha GR (1986) Estrogen stimulation of deoxyribonucleic acid synthesis in uterine epithelial cells which lack estrogen receptors. Endocrinology 119:390–396

    Google Scholar 

  • Bocquel MT, Kumar V, Stricker C, Chambon P, Gronemeyer H (1989) The contribution of the N- and C-terminal regions of steroid receptors to activation of transcription is both receptor and cell-specific. Nucleic Acids Res 17:2581–2595

    Google Scholar 

  • Casimiri V, Tath NC, Parvey H, Psychoyos A (1980) Effect of sex steroids on rat endometrial epithelium and stroma cultured separately. J Steroid Biochem 12:293–298

    Google Scholar 

  • Cunha GR, Shannon JM, Vanderslice KD, Sekkingstad M, Robby S (1982) radioautographic analysis of nuclear estrogen binding sites during postnatal development of the genital tract of female mice. J Steroid Biochem 17:281–286

    Google Scholar 

  • Das RM (1972) The effects of estrogen on the cell cycle in epithelial and connective tissues of the mouse uterus. J Endocrinol 55:21–30

    Google Scholar 

  • Das RM, Martin L (1973) Progesterone inhibition of mouse uterine epithelium proliferation. J Endocrinol 59:205–206

    Google Scholar 

  • Forabosco A, Sforza C, De Pol A, Vizzotto L, Marzona, Ferrario VF (1991) Morphometric study of the human neonatal ovary. Anat Rec 231:201–208

    Google Scholar 

  • Greco TL, Forlow JD, Duello TM, Gorski J (1991) Immunodetection of estrogen receptors in fetal and neonatal female mouse reproductive tracts. Endocrinology 129:1326–1332

    Google Scholar 

  • Greenwald GS, Roy SK (1994) Follicular development and its control. In: Knobil E, Neill JD (eds) The physiology of reproduction, vol 1. Raven Press, New York, pp 629–724

    Google Scholar 

  • Halpin DMG, Jones A, Fink G, Charlton HM (1986) Postnatal ovarian follicle development in hypogonadal (hpg) and normal mice and associated changes in the hypothalamic-pituitary ovarian axis. J Reprod Fertil 77:287–296

    Google Scholar 

  • Hanai T, Usuda N, Morita, T, Shimizu T, and Nagata T (1993) Proliferative activity in the kidneys of aging mice evaluated by PCNA/cyclin immunohistochemistry. Cell Mol Biol 39:181–191

    Google Scholar 

  • Haslam SZ (1986) Mammary fibroblast influence on normal mammary epithelial cell responses to estrogen in vitro. Cancer Res 46:310–316

    Google Scholar 

  • Hillier SG, Saunders PTK, White R, Paerker MG (1989) Oestrogen receptor mRNA and a related RNA transcript in mouse ovaries. J Mol Endocrinol 2:39–45

    Google Scholar 

  • Hinds PW, Mittnacht S, Dulic V, Reed SI, Winberg RA (1992) Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell 70:993–1006

    Google Scholar 

  • Iguchi T, Uchima F-DA, Ostrander PL, Bern HA (1983) Growth of normal mouse vaginal epithelial cells in and on collagen gels. Proc Natl Acad Sci USA 80:3743–3747

    Google Scholar 

  • Iwai T, Nanbu Y, Iwai M, Taii S, Fujii S, Mori T (1990) Immunohistochemical localization of oestrogen and progesterone receptors in the human ovary throughout the menstrual cycle. Virchows Arch [A] 417:369–375

    Google Scholar 

  • Kiss R, Lenglet G, Pasteels JL, Danguy A (1987a) Hormonal regulation of uterine epithelial cell proliferation. I. Effect of estradiol or progesterone administered separately. In Vivo 1:281–289

    Google Scholar 

  • Kiss R, Lenglet G, Pasteels JL, Danguy A (1987b) Hormonal regulation of uterine epithelial cell proliferation. II. Effect of estradiol or progesterone administered in combination. In Vivo 1:291–296

    Google Scholar 

  • Komatsu M, Fujita H (1978) Electron-microscopic studies on the development and aging of the oviduct epithelium of mice. Anat Embryol 152:243–259

    Google Scholar 

  • Korach KS, Horigome T, Tomooka Y, Yamashita S, Newbold RR, McLanchlan JA (1988) Immunodetection of estrogen receptor in epithelial and stromal tissues of neonatal mouse uterus. Proc Natl Acad Sci USA 85:3334–3337

    Google Scholar 

  • Mannan MA, O'Shaughnessy PJ (1991) Steroidogenesis during postnatal development in the mouse ovary. J Endocrinol 130:101–106

    Google Scholar 

  • McGrath CM (1983) Augmentation of the response of normal mammary cells to estradiol by mammary stroma. Cancer Res 43:1355–1360

    Google Scholar 

  • Miuras S, Burzio L, Koide SS (1972) Studies on deoxyribonucleic acid synthesis in uteri of immature mouse. Horm Metab Res 4:273–277

    Google Scholar 

  • Morita T, Usuda N, Hanai T, Nagata T (1994) Change of colon epithelium proliferation due to individual aging with PCNA/cyclin immunostaining comparing with 3H-thymidine radioautography. Histocheme 101:13–20

    Google Scholar 

  • Nagata T (1990) Principles and techniques of electron microscopic radioautography. In: World Health Organization (ed) Application of electron microscopy in biochemical research and diagnosis of human disease. WHO, Beijng, China, pp 139–158

    Google Scholar 

  • Nagata T (1991) Techniques and applications of electron microscopic radioautography in biomedical research. In: Mukherjee TMM, Swift JG (eds) World Health Organization Bi-regional Training Course on Electron Microscopy in Biomedical Research and Diagnosis of Human Disease. WHO, Adelaide, Australia, pp 73–90

    Google Scholar 

  • Nagata T (1992) Radiolabeling of soluble and insoluble compounds as demonstrated by light and electron microscopy. In: Wegmann RJ, Wegmann MA (eds) Recent advances in cellular and molecular biology, vol 6. Peeters Press, Leuven, Belgium, pp 9–21

    Google Scholar 

  • Nguyen BL, Giambiagi N, Mayrand C, Lecerf F, Pasqualini JR (1986) Estrogen and progesterone receptors in the fetal and newborn vagina of guinea pig: biological, morphological, and ultrastructural responses to tamoxifen and estradiol. Endocrinology 119:978–988

    Google Scholar 

  • Ogasawara Y, Okamoto S, Kitamura Y, Matsumoto K (1983) Proliferative pattern of uterine cells from birth to adulthood in intact, neonatally castrated and/or adrenalectomized mice, assayed by incorporation of [125I] iododeoxyuridine. Endocrinology 113:582–587

    Google Scholar 

  • Pedersen T (1969) Follicle growth in the immature mouse ovary. Acta Endocrinol 62:117–132

    Google Scholar 

  • Peters H (1969) The development of the mouse ovary from birth to maturity. Acta Endocrinol 62:98–116

    Google Scholar 

  • Press MF, Greene GL (1988) Localization of progesterone receptor with monoclonal antibody to the human progestin receptor. Endocrinology 122:1165–1175

    Google Scholar 

  • Press MF, Nousek-Goebl NA, Bur M, Greene GL (1984) Immunohistochemical assessment of estrogen receptor distribution in the human endometrium throughout the menstrual cycle. Lab Invest 51:495–503

    Google Scholar 

  • Sakamoto S, Abe A, Kudo H, Yamada N, Seki K, Okamoto R (1983) Effects of estrogen and progesterone on thymidine kinase activity in the immature rat uterus. Am J Obstet Gynecol 145:711–715

    Google Scholar 

  • Tomooka Y, Diaugustine RP, Malachlan JA (1986) Proliferation of mouse uterine epithelial cells in vitro. Endocrinology 118:1011–1018

    Google Scholar 

  • Wasseem NH, Lane DP (1990) Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nuclear form. J Cell Sci 96:121–129

    Google Scholar 

  • Weigel NL, Beck CA, Estes PA, Prendergast P, Altmann M, Christensen K, Edwards DP (1992) Ligands induce conformational changes in the carboxyl-terminus of progesterone receptors which are detected by a site-directed antipeptide monoclonal antibody. Mol Endocrinol 6:1585–1597

    Google Scholar 

  • Yamashita S, Newbold RR, McLanchlan JA, Korach S (1989) Developmental pattern of estrogen receptor expression in female mouse genital tracts. Endocrinology 125:2888–2896

    Google Scholar 

  • Yamashita S, Newbold RR, McLanchlan JA, Korach S (1990) The role of the estrogen receptor in uterine epithelial proliferation and cytodifferentiation in neonatal mice. Endocrinology 127:2456–2463

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, S. Relationship between cellular DNA synthesis, PCNA expression and sex steroid hormone receptor status in the developing mouse ovary, uterus and oviduct. Histochemistry 102, 405–413 (1994). https://doi.org/10.1007/BF00268912

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00268912

Keywords

Navigation