Changes in distribution of androgen receptor during maturation of rat ovarian follicles

Summary:

Sequential changes in androgen receptor (AR) distribution were investigated in rat ovarian follicles during their physiological development.

Mature female Wistar rats, exhibiting a regular 4-day oestrous cycle, were killed in succession on the day of oestrus, metoestrus, dioestrus, and pro-oestrus. Excised ovaries were submitted to immunohistochemical procedure in which polyclonal androgen receptor antibody, avidin-biotin-peroxidase complex, and DAB were used. Strong AR immunostaining was located predominantly in the nuclei of the granulosa layer of preantral and very early antral follicles, present in the ovaries at all stages of the oestrous cycle. At early oestrus a decline in AR was noted in the mural granulosa cells of presumably recruited early antral follicles. The decline involved the area of appearing pseudostratification. During metoestrus and dioestrus AR decline proceeded towards the antrum, but the antral regions connected with COC by strings of granulosa cells or lying in close proximity to COC were always strongly AR-positive. It was only on the day of pro-oestrus that AR was confined to COCs and a few antral cells bordering the antrum. These findings indicate that during the oestrous cycle AR decline starts in the mural granulosa cells of oestrous antral follicles beginning to differentiate and is completed at pro-oestrus, but even before ovulation it does not extend to COC. The persistence of AR immunostaining in the latter region suggests that androgens can play here a paracrine role especially before ovulation. Atretic follicles showed a different pattern of AR distribution, dependent on their stage of development and the advancement of this process.

Androgen receptors - developing follicles - COCs

References

• 1 Alexander N J, Kim H K, Blye R R, Blackmore P F. Steroid specificity of the human sperm membrane progesterone receptor.  Steroids. 61 116-125 1996; 
• 2 Amsterdam A, Rotmensch S. Structure-function relationships during granulosa cell differentiation.  Endocrine Reviews. 8 309-337 1987; 
• 3 Bar-Ami S. Increasing progesterone secretion and 3β-hydroxysteroid dehydrogenase activity of human cumulus cells and granulosa lutein cells concurrent with successful fertilisation of the corresponding oocyte.  J Steroid Biochem Molec Biol. 51 299-305 1994; 
• 4 Butcher R L, Collins W L, Fugo N W. Plasma concentration of LH, FSH, prolactin, progesterone estradiol 17-β throughout the 4-day estrous cycle of the rat.  Endocrinology. 94 1704-1708 1974; 
• 5 Butcher R L, Kirkpatrick-Keller D. Patterns of follicular growth during the four-day estrous cycle of the rat.  Biol Reprod. 31 280-286 1984; 
• 6 Carrizo D G, Rastrilla A M, Telleria C M, Aquado L I. Androstenedione stimulates progesterone production in corpora lutea of pregnant rats: An effect not mediated by oestrogen.  J Steroid Biochem Molec Biol. 51 3-4 1994; 
• 7 Chadha S, Pache T D, Huikeshoven F JM, Brinkman A O, van der Kwast T H. Androgen receptor expression in human ovarian and uterine tissue of long-term androgen-treated transsexual women.  Hum Pathol. 25 1198-1204 1994; 
• 8 Driancourt M A, Gougeon A, Royere D, Thibault Ch. Ovarian function. In: Thibault Ch, Levasseur M, Hunter RHF (eds). Reproduction in mammals and men Elipses Parts pp 281-305 1993
• 9 Eppig J J, Wigglesworth K, Pendola F, Hirao Y. Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells.  Biol Reprod. 56 976-984 1997; 
• 10 Fortune J E. Ovarian follicular growth and development in mammals.  Biol Reprod. 50 225-231 1994; 
• 11 Gregoraszczuk E. The interaction of testosterone and gonadotropins in stimulating estradiol and progesterone secretion by cultures of corpus luteum cells isolated from pigs in early and midluteal phase.  Endocrinol Japan. 38 229-237 1991; 
• 12 Hillier S G, Tetsuka M, Fraser H M. Location and developmental regulation of androgen receptor in primate ovary.  Human Reprod. 12 107-111 1997; 
• 13 Hirai M, Hirata S, Osada T, Hagihara K, Kato J. Androgen receptor mRNA in the rat ovary and uterus.  J Steroid Biochem Mol Biol. 49 1-7 1994; 
• 14 Hirshfield A N, Midgley R. Morphometric analysis of follicular development in the rat.  Biol Reprod. 19 597-605 1978; 
• 15 McNatty K P, Smith D M, Markis A, Osathanondh R, Ryan K J. Steroidogenesis by human oocyte-cumulus complexes in vitro.  Steroids. 35 643-651 1980; 
• 16 Nequin L G, Alvarez J, Schartz N B. Measurement of serum steroid and gonadotropin levels and uterine and ovarian variables throughout 4 day and 5 day estrous cycle in the rat.  Biol Reprod. 20 659-670 1979; 
• 17 Regucka J, Szołtys M, Wójtowicz A, Walocha A. Effects of testosterone, FSH, and LH on oestradiol and progesterone secretion by preovulatory cumulus oophorus complexes of the rat.  Exp Clin Endocrinol Diabetes. 107 44-48 1999; 
• 18 Richards J S. Maturation of ovarian follicles: Actions and interactions of pituitary and ovarian hormones on follicular cell differentiation.  Physiol Rev. 6 51-89 1980; 
• 19 Richards J S. Hormonal control of gene expression in the ovary.  Endocrine Reviews. 15 725-751 1994; 
• 20 Salustri A, Yanagishita M, Underhill C B, Laurent T C, Hascall V C. Localization and synthesis of hyaluronic acid in the cumulus cells and mural granulosa cells of the preovulatory follicle.  Dev Biol. 151 541-551 1992; 
• 21 Słomczyńska M, Szołtys M. Immunohistochemical localization of androgen receptor (AR) in rat ovary.  Folia Histochem Cytobiol. 35 101-102 1997; 
• 22 Szołtys M. Oestrogens and progestagens in rat ovarian follicles during the oestrous cycle.  J Reprod Fert. 63 221-224 1981; 
• 23 Szołtys M, Galas J, Jabłonka A, Tabarowski Z. Some morphological and hormonal aspects of ovulation and superovulation.  J Endocrinol. 141 91-100 1994; 
• 24 Szołtys M, Słomczyńska M, Wójtowicz A, Pierściński A. Subpopulations of the granulosa layer differentiated by histo- and immunocytochemical methods in the preovulatory follicle of the rat.  Folia Histochem Cytobiol. 37 91-92 1999; 
• 25 Suzuki T, Sasano H, Kimura N, Tamura M, Fukaja T, Yajima A, Nagura H. Immunohistochemical distribution of progesterone, androgen and oestrogen receptors in the human ovary during the menstrual cycle: relationship to expression of steroidogenic enzymes.  Hum Reprod. 9 1589-1595 1994; 
• 26 Takeda H, Chodak G, Mutchnik S, Nakamoto T, Chang C. Immunohistochemical localization of androgen receptors with mono- and polyclonal antibodies to androgen receptor.  J Endocrinol. 126 17-25 1990; 
• 27 Tetsuka M, Hillier S G. Androgen receptor gene expression in rat granulosa cells: the role of follicle-stimulating hormone and steroid hormones.  Endocrinology. 137 4392-4397 1996; 
• 28 Tetsuka M, Hillier S G. Differential regulation of aromatase and androgen receptor in granulosa cells.  J Steroid Biochem Molec Biol. 61 233-239 1997; 
• 29 Tetsuka M, Whitelaw P F, Bremner W J, Millar M R, Smyth C D, Hillier S G. Developmental regulation of androgen receptor in rat ovary.  J Endocr. 145 535-543 1995; 
• 30 Wesley M, Garret H, Guthrie D. Expression of androgen receptors and steroidogenic enzymes in relation to follicular growth and atresia following ovulation in pigs.  Biol Reprod. 55 949-955 1996; 
• 31 Wójtowicz A, Szołtys M. Preovulatory secretion of steroids by cultured cumulus oophorus complexes of the rat. Effects of FSH and LH.  Exp Clin Endocrinol Diabetes. 106 499-504 1998; 
• 32 Zoller L C. Quantitative analysis of the membrana granulosa in developing and ovulatory follicles.  In: Makabe G, Motta PM (eds). Ultrastructure of the ovary Kluwer Academic Publishers pp 73-89 1991