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Effects of Growth Hormone, Activin, and Follistatin on the Development of Preantral Follicle from Immature Female Mice

Department of Obstetrics and Gynecology, Gunma University School of Medicine, 3–39-15 Maebashi, Gunma 371, Japan

Address all correspondence and requests for reprints to: Dr. Hideki Mizunuma, Department of Obstetrics and Gynecology, Gunma University School of Medicine, 3–39-22 Showa-machi, Maebashi, Gunma 371, Japan. E-mail: mizunuma{at}news.sb.gunma-u.ac.jp

	Abstract

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The aim of this study was to investigate whether GH and insulin-like growth factor I (IGF-I) are involved in preantral folliculogenesis and, if so, to clarify the relationship between GH/IGF-I and activin/follistatin (FS) systems in immature female mice. Ovaries were obtained from 11-day-old mice, and preantral follicles, 100–105 µm in diameter, were mechanically isolated and selected for culture. Ten preantral follicles per well were cultured with different quantities and combinations of additives as follows: no additives (control), recombinant human FSH (rhFSH), IGF-I, recombinant human GH (rhGH), activin A, and recombinant human FS (rhFS). Mean diameters of the follicles were measured daily, and estradiol and immunoreactive inhibin levels in the cultured medium were assayed by RIA on day 4. rhGH showed stimulatory effects on the follicular diameter and the secretion of estradiol and immunoreactive inhibin. These effects were augmented by the presence of IGF-I and activin A. IGF-I alone did not show any stimulatory effect. The addition of rhFSH to activin A or to rhGH and activin A promoted preantral follicular growth and hormone production. On the other hand, GH- or activin-stimulated follicular growth was suppressed by rhFS in a dose-dependent manner. These results indicate that activin A and rhGH may play an important role in controlling earlier phases of follicular development during the infantile period, which is considered to be gonadotropin independent.

	Introduction

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FOLLICULOGENESIS is a process of follicular growth characterized by morphological changes accompanied by functional development and has been shown to be regulated primarily by the pituitary gonadotropin, FSH. However, it has been suggested that folliculogenesis up to the antrum formation stage is independent of FSH. FSH gene knockout mice have follicular growth to the multilayer preantral follicle stage (1), confirming that the early stage of folliculogenesis is stimulated by some other factors. Recent studies have shown that folliculogenesis is under the influence of both intra- and extraovarian factors and that intra-ovarian factors sometimes override the action of FSH, although the physiological significance of these factors has not been fully clarified (2). We have shown that activin A, an ovarian peptide, promotes the folliculogenesis of preantral follicles from immature female mice and that activin has a synergistic action with FSH (3). Activin has a potent effect on follicular growth through an autocrine-paracrine action. Activin stimulates the differentiation of granulosa cells (4, 5, 6) as well as the proliferation of granulosa cells (7), and the action of activin is neutralized by follistatin (FS), another gonadal protein.

GH and insulin-like growth factor I (IGF-I), on the other hand, are potent extra- and intraovarian factors, respectively, that play an important role in the regulation of follicular function. Suppression of endogenous GH release delays the onset of puberty in female rats (8, 9), and GH administration to congenital GH-deficient rats restores the time of the onset of puberty (10). In in vitro studies, GH and IGF-I augment FSH-stimulated LH receptor formation, progesterone biosynthesis, and cAMP production in porcine or rat granulosa cells (11, 12, 13). Although GH stimulates IGF-I production by granulosa cells, and IGF-I is capable of augmenting granulosa cell function, it is still unclear whether GH has a direct action on follicular function (14). In addition, the effects of GH and IGF-I on early folliculogenesis up to the antrum formation stage are entirely unknown.

As a result, the present study was designed to investigate whether GH and IGF-I are involved in preantral folliculogenesis and, if so, to clarify the relationship between GH/IGF-I and activin/FS systems in immature female mice. We used the in vitro preantral follicle culture system, as preantral follicles obtained from immature mice have the oocyte surrounded by layers of granulosa cells and an intact basal lamina with thecal cells and show significant growth in response to activin, but not FSH (3).

	Materials and Methods

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Chemicals
Recombinant human GH (rhGH) was provided by Serono Laboratories Co. (Geneva, Switzerland). Human erythroid differentiation factor/activin A (activin A) was prepared as described previously (15). Recombinant human follicle-stimulating hormone (rhFSH) was obtained from Organon Co. (Oss, The Netherlands). Recombinant human IGF-I was obtained from Sigma Chemical Co. (St. Louis, MO). Recombinant human FS (rhFS) with 288 amino acids was provided by the National Hormone and Pituitary Program, NIDDK.

Animals
BDF1 hybrid mother mice with 7-day-old infant female mice were purchased from Japan Charles River (Tokyo, Japan) and housed in a temperature (24–26 C)- and light-controlled room with a 14-h light, 10-h dark photoperiod in accordance with the principles of the Animal Science Center of the Gunma University School of Medicine. The mother mice were given food and water ad libitum, and the infant mice were nursed for 4 days. Eleven-day-old immature female mice, weighing approximately 6.0–6.2 g, were killed by cervical dislocation.

Preantral follicle isolation and culture
Preantral follicles were prepared as described previously (3). Briefly, ovaries, weighing approximately 0.44–0.49 mg, were removed aseptically from the 11-day-old immature female mice and placed in 15-mm diameter Falcon plastic petri dishes (Falcon 3037, Becton Dickinson Co., Rutherford, NJ) filled with DMEM (Life Technologies, Tokyo, Japan) at room temperature. After removing the surrounding tissue, the ovaries were microdissected using 2 27-gauge needles attached to 1-ml syringes under the stereomicroscope (Olympus SZH, Olympus Co., Tokyo, Japan), and approximately 20 preantral follicles were mechanically isolated from 1 ovary in a humidified chamber with 5% CO₂ in the air at 37 C.

Ten preantral follicles, 100–105 µm in diameter with one or two layers of granulosa cells around the oocyte and an intact basal lamina with thecal cells, were transferred into a Falcon plastic petri dish filled with 1 ml serum-free DMEM supplemented with 6.25 µg/ml insulin, 6.25 µg/ml transferrin, 6.25 ng/ml selenious acid, 5.35 µg/ml linoleic acid, 0.15% BSA, 15 mM HEPES, 45 µg/ml penicillin G, 350 µg/ml streptomycin, and 1.75 µg/ml amphotericin B. Ten preantral follicles were cultured in a humidified chamber with 5% CO₂ in the air at 37 C for 4 days. Hormones were added to the same conditioned medium on day 0 in the indicated concentrations and combinations. Each experiment was repeated from 5–10 times.

Measurement of follicular diameter and hormone assay
The mean diameters of the preantral follicles in two dimensions were measured daily using an inverted microscope (Olympus IMT-2, Olympus Co.).

To determine the levels of estradiol (E₂) and immunoreactive (IR-) inhibin, the cultured medium was collected on day 4 and stored at -20 C until assayed. All samples were assayed in duplicate by RIA. E₂ levels were determined by using anti-E₂ antiserum supplied by Dr. W. F. Crowley, Jr. (16), and radioactive tracer estradiol-6-(O-carboxymethyl) oximino-(2-[¹²⁵I)iodohistamine) (Amersham, Aylesbury, UK). IR-inhibin concentrations were measured by double antibody RIA using rabbit antiserum against bovine follicular fluid inhibin, as described previously (17). The intra- and interassay coefficients of variation for E₂ and IR-inhibin were 2.2% and 3.6%, and 4.7% and 6.7%, respectively.

Statistics
Results were presented as the mean ± SEM. Statistical analysis was performed by one-way ANOVA, followed by Scheffe’s multiple comparison test. P < 0.05 was considered statistically significant.

	Results

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Daily changes in follicular diameter of preantral follicles cultured with the medium alone (control) or with the addition of rhFSH, rhGH, IGF-I, or activin A are shown in Fig. 1. As there was no significant indication of oocyte hypertrophy, the changes in follicular diameter could be accounted for by an increase in the number of granulosa cells. Preantral follicles cultured with medium alone, rhFSH, or rhIGF-I did not show a significant increase in size during 4 days of culture, whereas those cultured with rhGH and activin A showed a significant increase. Because there were no time components in follicular growth, follicular diameter on day 4 in each treatment group is represented in Fig. 2. Follicular diameter in rhFSH- and IGF-I-treated groups was not statistically different from that in the controls, but that in rhGH- and activin A-treated groups was significantly greater than the control values. The effect of rhFSH on follicular growth was enhanced by coincubation with IGF-I and activin A, but not with rhGH. Although rhGH caused a significant increase in follicular diameter, the effect of rhGH was enhanced by IGF-I and activin A. Activin A enhanced the effects of rhFSH, rhGH, and their combination, but activin A did not augment the effect of IGF-I. These results indicate that local ovarian regulators, such as activin A or IGF-I, have a potent stimulatory effect with pituitary hormones on the follicular development of preantral follicles from immature mice, but there is no synergistic action between local regulators. Furthermore, the actions of pituitary hormones are augmented by ovarian local regulators, but pituitary hormones do not act with each other on preantral follicles from immature mice.

View larger version (27K): [in this window] [in a new window]   Figure 1. Changes of preantral follicular diameters cultured with rhFSH, rhGH, IGF-I, and activin A for 4 days. Values in parentheses are the number of cultured preantral follicles. The data shown are the mean and SEM. *, P < 0.01 vs. day 0. , P < 0.0001 vs. day 0. a, P < 0.01 vs. control (medium alone). b, P < 0.0001 vs. control.

View larger version (37K): [in this window] [in a new window]   Figure 2. Follicular diameter of preantral follicles cultured for 4 days with rhFSH, rhGH, IGF-I, activin A, and the combination of each. The data shown are mean and SEM. Vertical bars indicate SEs. Values in parentheses are the number of cultured preantral follicles. a, P < 0.001 vs. control (medium alone). b, P < 0.0001 vs. 1 mIU rhGH and 1 mIU rhGH plus 100 mIU rhFSH. c, P < 0.0001 vs. 100 ng activin A and 100 ng activin A plus 100 ng IGF-I. d, P < 0.0001 vs. 100 ng activin A plus 100 mIU rhFSH and 1 mIU rhGH plus 100 ng activin A.

View larger version (28K): [in this window] [in a new window]   Figure 3. Neutralizing effect of FS on activin A and rhGH-stimulated follicular growth. The data shown are the mean and SEM diameter on day 4. Vertical bars indicate SEs. Values in parentheses are the number of cultured preantral follicles.

	Discussion

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There may be two separate pathways for the action of GH at the ovarian level (19). GH may interact with putative GH receptor and accomplish its effects. Alternatively, GH may act indirectly by stimulating ovarian IGF-I gene expression, which, in turn, mediates GH effects. Gong et al. (20) indicated in an in vivo study that bovine GH increased the population of antral follicles in mature heifer, and they concluded that a direct effect of GH at the ovarian level could not be excluded, although it is possible that GH may act via an increased peripheral IGF-I concentration. GH stimulates the production of IGF-I and its messenger RNA (mRNA) in porcine granulosa cells and rat ovary (21, 22, 23). In addition, the level of granulosa cell IGF-I mRNA is stimulated by E₂, GH, dexamethasone, and insulin, but FSH has little effect (24, 25). IGF-I stimulates FSH-induced progesterone and E₂ biosynthesis, acquisition of LH receptors, proteoglycan synthesis, and inhibin production (13, 26, 27). These results suggest that IGF-I may be the core of the GH/IGF-I axis in the context of follicular development. However, the present study was not able to show the direct effect of IGF-I on follicular growth or on E₂ or IR-inhibin secretion, suggesting that the action of GH on the follicular growth of preantral follicles is direct. Of interest, IGF-I showed a stimulatory effect on follicular growth when administered with FSH. It has been shown that the action of IGF-I on granulosa cell function is FSH dependent (13). The present study cannot clarify how primary follicles become capable of responding to FSH when cocultured with IGF-I, but it is suggested that the actions of GH and IGF-I are different in the early stage of folliculogenesis. GH has both somatogenic and lactogenic actions in rats (28), but it seems that the effect of GH on follicular growth detected in this study was through somatogenic action, because bovine PRL at doses of 10–1000 µg/ml did not have any effect on follicular growth (data not shown). Recently, Apa et al. (14) have demonstrated that GH directly stimulated androgen synthesis by rat thecal-interstitial cells because the addition of anti-IGF-I antibodies to the GH culture did not modify the GH effect. Our results support this finding.

We have shown the paradoxical action of activin A on folliculogenesis between immature and adult mice (3). Whereas activin A stimulated preantral follicular growth in follicles from immature female mice, activin A had no effect on preantral follicles from adult mice and additionally suppressed follicular growth stimulated by FSH (3). Because FSH did not show an increase in follicular growth, activin A has been shown to be involved in gonadotropin-independent follicular growth during the infantile period. The present study further suggests that GH may play a part in gonadotropin-independent follicular growth. Of interest is the finding that FSH or IGF-I did not show a stimulatory effect on the growth of follicles from immature mice. However, FSH had a synergistic effect with putative intraovarian factors such as activin A and IGF-I, whereas IGF-I had an effect with FSH and GH, both of which are categorized as extraovarian factors. On the other hand, there was no synergistic effect between GH and FSH or between IGF-I and activin A. These results suggest that the synergistic action is functioning only between intraovarian factors and extraovarian factors. The mechanisms that enhance the actions of intra- or extraovarian factors are not clarified in this study, but it has been shown that activin enhances FSH action through increasing the number of FSH receptors (29).

This is the first report to show that FS blocks the effect of GH on preantral folliculogenesis of immature mice. FS is a single chain glycoprotein that can selectively suppress the secretion of FSH by the pituitary gland, and FS can inhibit activin-induced cell growth and the formation of follicles (3, 7). FS binds to activin and limits the bioavailability of the action, and the suppressive effect of FS is considered to be mainly the neutralizing of activin (29). Therefore, it is suggested that the effect of GH on folliculogenesis is potentially mediated by an activin pathway; however, whether GH stimulates activin A production in granulosa cells remains unclear. It is also possible that FS may have a direct inhibitory effect on GH action independent of its activin-binding activity. This possibility is based upon the different responses of steroid production by rat granulosa cells to activin and FS administration (30), but to date, there have been no reports of receptor for FS or that FS can bind GH. FS mRNA is not detected in primordial or primary follicles and first becomes detectable in granulosa cells of secondary follicles (31); therefore, it is presumed that FS can elicit significant roles in the early folliculogenesis by modulating the action of GH by unknown pathways. In addition, the physiological significance of GH and that of activin seem to be different. As shown in Table 1, E₂ secretion was significantly increased by the addition of activin A and FSH, to a greater degree than by the addition of GH and FSH, indicating that activin A is involved more profoundly than GH in the differentiation of granulosa cells.

Thus, the present study has demonstrated that activin A and GH play an important part in controlling the earlier phases of follicular development during the infantile period that has previously been considered to be gonadotropin independent. FSH and IGF-I are also involved in the follicular development of preantral follicular growth from immature mice, but the actions of FSH and IGF-I were GH and activin A dependent. The physiological significance of this interaction remains unclarified, but it functions to guarantee follicular growth in certain conditions such as GH deficiency, as previously reported. Indeed, it has been well established that folliculogenesis occurs in rats with a congenital GH deficit (32) and in women with isolated IGF-I deficiency (33). Although the present study could not prove a direct linkage between GH and activin, the effects of both activin and GH were completely blocked by FS, suggesting that GH, activin, and FS interaction plays an important role in the intraovarian control of the folliculogenesis of immature female mice.

	Acknowledgments

 
We thank Dr. Yuzuru Eto (Ajinomoto Central Research Laboratories, Kawasaki, Japan) for his kind donation of rh-activin A, and Dr. Yoshihisa Hasegawa (Kitasato University School of Veterinary and Animal Sciences, Kitasato, Japan) for his expert advice. We also thank Miss Y. Hayashi and Miss T. Ishihara for their assistance.

Received September 11, 1997.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Kumar TR, Wang Y, Lu N, Matzuk MM 1997 Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 15:201–204[CrossRef][Medline]
2. Greenwald GS, Roy SK 1994 Follicular development and its control. In: Knobil E, Neill JD (eds) The Physiology of Reproduction, ed 2, Raven Press, New York, vol 1:629–724
3. Yokota H, Yamada K, Liu XW, Kobayashi J, Abe Y, Mizunuma H, Ibuki Y 1997 Paradoxical action of activin A on folliculogenesis in immature and adult mice. Endocrinology 138:4572–4576[Abstract/Free Full Text]
4. Hutchinson LA, Findlay JK, de Vos FL, Robertson DM 1987 Effects of bovine inhibin, transforming growth factor-beta and bovine Activin-A on granulosa cell differentiation. Biochem Biophys Res Commun 146:1405–1412[CrossRef][Medline]
5. Sugino H, Nakamura T, Hasegawa Y, Miyamoto K, Abe Y, Igarashi M, Eto Y, Shibai H, Titani K 1988 Erythroid differentiation factor can modulate follicular granulosa cell functions. Biochem Biophys Res Commun 153:281–288[CrossRef][Medline]
6. Hasegawa Y, Miyamoto K, Abe Y, Nakamura T, Sugino H, Eto Y, Shibai H, Igarashi M Induction of follicle stimulating hormone receptor by erythroid differentiation factor on rat granulosa cell. Biochem Biophys Res Commun 156:668–674
7. Li R, Phillips DM, Mather JP 1995 Activin promotes ovarian follicle development in vitro. Endocrinology 136:849–856[Abstract]
8. Ramaley JA, Phares CK 1980 Delay of puberty onset in females due to suppression of growth hormone. Endocrinology 106:1989–1993[Abstract/Free Full Text]
9. Advis JP, White SS, Ojeda SR 1981 Activation of growth hormone short loop negative feedback delays puberty in the female rat. Endocrinology 108:1343–1352[Abstract/Free Full Text]
10. Bartke A 1964 Histology of the anterior hypophysis, thyroid and gonads of two types of dwarf mice. Anat Rec 149:225–229[CrossRef][Medline]
11. Jia XC, Kalmijn J, Hsueh AJ 1986 Growth hormone enhances follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells. Endocrinology 118:1401–1409[Abstract/Free Full Text]
12. Hutchinson LA, Findlay JK, Herington AC 1988 Growth hormone and insulin-like growth factor-1 accelerate PMSG-induced differentiation of granulosa cells. Mol Cell Endocrinol 55:61–69[CrossRef][Medline]
13. Giudice LC 1992 Insulin-like growth factors and ovarian follicular development. Endocr Rev 13:641–669[Abstract/Free Full Text]
14. Apa R, Caruso A, Andreani CL, Miceli F, Lazzarin N, Mastrandrea M, Ronsisvalle E, Mancuso S, Lanzone A 1996 Growth hormone stimulates androsterone synthesis by rat theca-interstitial cells. Mol Cell Endocrinol 118:95–101[CrossRef][Medline]
15. Murata M, Onomichi K, Eto Y, Shibai H, Muramatsu M 1988 Expression of erythroid differentiation factor (EDF) in Chinese hamster ovary cells. Biochem Biophys Res Commun 151:230–235[CrossRef][Medline]
16. Crowley Jr WF, Beitins IZ, Vale W, Kliman B, Rivier J, Rivier C, McArthur JW 1980 The biologic activity of a potent analogue of gonadotropin-releasing hormone in normal and hypogonadotropic men. N Engl J Med 302:1052–1057[Abstract]
17. Hamada T, Watanabe G, Kokuho T, Taya K, Sasamoto S, Hasegawa Y, Miyamoto K, Igarashi M 1989 Radioimmunoassay of inhibin in various mammals. J Endocrinol 122:697–704[Abstract/Free Full Text]
18. Adashi EY 1993 The intraovarian insulin-like growth factor system. In: Adashi EY, Leung PCK (eds) The Ovary. New York, pp 319–335
19. Katz E, Ricciarelli E, Adashi E 1993 The potential relevance of growth hormone to female reproductive physiology and pathophysiology. Fertil Steril 59:8–34[Medline]
20. Gong JG, Bramley T, Webb R 1991 The effect of recombinant bovine somatotropin on ovarian function in heifers: follicular populations and peripheral hormones. Biol Reprod 45:941–949[Abstract]
21. Davoren JB, Hsueh AJ 1986 Growth hormone increases ovarian levels of immunoreactive somatomedin C/insulin-like growth factor I in vivo. Endocrinology 118:888–890[Abstract/Free Full Text]
22. Hsu CJ, Hammond JM 1987 Concomitant effects of growth hormone on secretion of insulin-like growth factor 1 and progesterone by cultured porcine granulosa cells. Endocrinology 121:1343–1348[Abstract/Free Full Text]
23. Hynes MA, Van Wyk JJ, Brooks PJ, D’Ercole AJ, Jansen M, Lund PK 1987 Growth hormone dependence of somatomedin-C/insulin-like growth factor 1 and insulin-like growth factor 2 messenger ribonucleic acids. Mol Endocrinol 1:233–242[Abstract/Free Full Text]
24. Hernandez ER, Roberts CT, LeRoith D, Adashi EY 1989 Rat ovarian insulin-like growth factor I (IGF-I) gene expression is granulosa cell-selective: 5'-unitranslated mRNA variant representation and hormonal regulation. Endocrinology 125:572–574[Abstract/Free Full Text]
25. Botero LF, Roberts CT, LeRoith D, Adashi EY, Hernandez ER 1993 Insulin-like growth factor I gene expression by primary cultures of ovarian cells: insulin and dexamethasone dependence. Endocrinology 132:2703–2708[Abstract/Free Full Text]
26. Ojeda SR, Jameson HE 1977 Developmental patterns of plasma and pituitary growth hormone (GH) in the female rat. Endocrinology 100:881–889[Abstract/Free Full Text]
27. Zhang ZW, Carson RS, Herington AC, Lee VWK, Burger HG 1987 Follicle-stimulating hormone and somatomedin-C stimulate inhibin production by rat granulosa cells in vitro. Endocrinology 120:1633–1638[Abstract/Free Full Text]
28. Ranke MB, Stanley CA, Tenore A, Rodbard D, Bongiovanni AM, Parks JS 1976 Characterization of somatogenic and lactogenic binding sites in isolated rat hepatocytes. Endocrinology 99:1033–1045[Abstract/Free Full Text]
29. Xiao S, Robertson DM, Findlay JK 1992 Effects of activin and follicle-stimulating hormone (FSH)-suppressing protein/follistatin on FSH receptors and differentiation of cultured rat granulosa cells. Endocrinology 131:1009–1016[Abstract/Free Full Text]
30. Findlay JK 1993 An update on the roles of inhibin, activin, and follistatin as local regulators of folliculogenesis. Biol Reprod 48:15–23[Abstract]
31. Nakatani A, Shimasaki S, Depaolo LV, Erickson GF, Ling N 1991 Cyclic changes in follistatin messenger ribonucleic acid and its protein in the rat ovary during the estrous cycle. Endocrinology 129:603–611[Abstract/Free Full Text]
32. Ozawa K, Mizunuma H, Ozawa H, Ibuki Y 1996 Recombinant human growth hormone acts on intermediate-sized follicles and rescues growing follicles from atresia. Endocr J 43:87–92[Medline]
33. Dor J, Ben-Shlomo I, Lunenfeld B, Pariente C, Levran D, Karasik A, Seppala M, Mashiach S 1992 Insulin-like growth factor-I (IGF-I) may not be essential for ovarian follicular development: evidence from IGF-I deficiency. J Clin Endocrinol Metab 74:539–542[Abstract]

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