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Biology of Reproduction 60, 78-84 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Secretion of Ovarian Inhibin and Its Physiologic Roles in the Regulation of Follicle-Stimulating Hormone Secretion during the Estrous Cycle of the Female Guinea Pig1

FangXiong Shia, Manao Ozawaa, Hisashi Komurab, PeiXin Yanga, Amanda L. Trewinc, Reinhold J. Hutzc, Gen Watanabea, and Kazuyoshi Taya2,a

a Laboratory of Veterinary Physiology, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan b Institute of Environmental Toxicology, Tokyo 187-0011, Japan c Department of Biological Sciences, University of Wisconsin-Milwaukee, Wisconsin 53201-0413


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
To characterize inhibin secretion during the estrous cycle in guinea pigs, the concentrations of plasma inhibin, estradiol, progesterone, and FSH were determined. A significant positive correlation was observed between inhibin and estradiol throughout the estrous cycle. Plasma inhibin and estradiol started to increase a few days before ovulation (Day 0 = day of estimated ovulation), and decreased after ovulation. These two hormones remained low during the luteal phase. The immunoreactivity of inhibin {alpha}, ßA, and ßB subunits was colocalized in the granulosa cells of one or two healthy large follicles in the ovary before ovulation. There was no positive reaction of inhibin {alpha} and ß subunits in the corpora lutea or other follicles. Ovariectomy resulted in an abrupt decrease in plasma inhibin and a significant increase in plasma FSH. Injection of anti-inhibin serum into adult female guinea pigs induced an elevation in plasma FSH in a dose-dependent manner. This report presents the first description of sequential changes in plasma inhibin and estradiol during the estrous cycle of guinea pigs. Results suggest that inhibin is secreted mainly by granulosa cells of a few healthy large follicles in the ovary and that it plays an important role in the regulation of FSH secretion during the estrous cycle in guinea pigs.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Guinea pigs, unlike other rodents, i.e., rats, mice, and hamsters, exhibit a prolonged luteal phase after spontaneous ovulation of 2–4 oocytes and thus have an extended ovarian cycle of 16–19 days duration similar to that observed in ruminants [1]. The guinea pig also shows the same biphasic pattern of follicular development [2, 3] as the cow [4] and sheep [5]. The guinea pig is thus a good animal model for study in the field of reproduction of large animals [1, 3]. In addition, our previous study [6] demonstrated that polycystic ovaries in guinea pigs similar to the polycystic ovarian syndrome (PCOS) in humans can easily be induced by treatment with estradiol-17ß. The guinea pig, therefore, is also a good animal model for study of PCOS in humans. Although the guinea pig is one of the most commonly used experimental animals in the field of biomedical research, there is a relative lack of knowledge of reproductive physiology in this species.

Ovarian inhibin is composed of disulfide-bonded {alpha} and ß-subunits. Combination of an {alpha}-subunit with either ß subunit ({alpha}/ßA or {alpha}/ßB) forms an inhibin molecule with potent bioactivity for inhibiting FSH secretion. Activin, on the other hand, a homodimer of the ß subunits (ßA/ßA, ßA/ßB, or ßB/ßB), has a bioactivity opposite that of inhibin and is a known stimulator of FSH secretion [7]. All three inhibin/activin subunits are encoded by separate mRNAs [8, 9] expressed in granulosa cells under the control of FSH. In the female rat [10–12] and hamster [13], inhibin secretion increases during follicular maturation and decreases abruptly at ovulation. Although a number of studies have described the immunohistochemical localization of inhibin in rats [7], hamsters [14], and humans [15–17], there are still no data on their immunohistochemical localization in guinea pigs.

Gonadal steroids have repeatedly been shown to be the primary regulators of both GnRH and gonadotropins in mammals. Several studies have delineated the pattern of progesterone secretion during the estrous cycle of guinea pigs [18–22], but changes in cyclic secretion of ovarian estrogens have received very little attention in this species. Some researchers tried to measure circulating estradiol levels but failed because of inadequate assay sensitivity [3, 22], possibly due to the very low circulating estradiol in guinea pigs [23, 24]. Joshi et al. [25] have determined the concentrations of estradiol in the ovarian venous plasma by RIA, since these concentrations were higher than those in the peripheral blood.

In the present study, we used RIAs to measure the concentrations of plasma FSH, inhibin, estradiol, and progesterone, and used immunohistochemistry and ovariectomy experiments to determine the secretory source of the inhibin. We also used the immunoneutralization of endogenous inhibin by injection of anti-inhibin serum to examine the role of inhibin in the regulation of FSH secretion during the estrous cycle in guinea pigs.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Animals and Sample Collection

Adult female guinea pigs of the Hartley strain (Saitama Experimental Animal Supply Co., Ltd., Saitama, Japan) were used at 3 mo of age. They were housed under controlled lighting (lights-on 0500–1900 h) and were provided with commercial pellets and tap water ad libitum. Estrous cycles were recorded by daily examination of the vaginal membrane, and smears were taken by lavage whenever the vagina was open. The day of ovulation, estimated as the day when maximal cornification was seen in the smear before the ovulatory influx of leukocytes, was designated Day 0 of the cycle [3, 19, 20, 26].

For characterization of the hormonal profile during the estrous cycle, blood samples from 85 guinea pigs (5 animals per day) were collected into heparinized centrifuge tubes by the intracardiac method under ether anesthesia on the morning of various days after estrus with respect to vaginal cytology.

To confirm the source of plasma inhibin, five adult female guinea pigs were bilaterally ovariectomized under ether anesthesia. Twenty-four hours before each experiment, a cannula (Dow Corning Co., Midland, MI) was inserted into the atrium via the external jugular vein in each animal for drawing blood samples. Two-milliliter blood samples were collected through the catheter just before (0) ovariectomy and at 0.5, 1, 3, 6, 12, 24, 36, and 48 h after ovariectomy. The plasma was separated immediately by centrifugation, and the red blood cells were suspended with heparinized 0.9% NaCl solution and immediately injected back to the animal through the catheter.

In the immunoneutralization experiment, 18 female guinea pigs received an s.c. implant (silicone elastomer [Silastic] tubing, 1.0 cm long, 0.4 cm i.d.; Dow Corning Co.) filled with crystalline progesterone for 23–33 days. In earlier studies, this treatment produced luteal levels of circulating progesterone (7.9 ± 0.9 ng/ml, n = 9) and prevented ovulation [27, 28]. Animals given this treatment ovulate within 6 days after removal of the progesterone capsules [28]. These results indicate that this is a practical method for study of follicular function during the luteal phase and also during the rapid growth of follicles before ovulation in the guinea pig. In our study, the animals, which had received cannula in the right atrium, were placed into three groups, which received injections through the cannula of 1.0 ml nonimmune goat serum (NGS; group 1), 0.5 ml anti-inhibin serum and 0.5 ml NGS (group 2), or 1.0 ml anti-inhibin serum (group 3). Blood samples were collected through an inserted catheter at 0, 6, 12, 24, and 48 h after injections. The plasma samples were stored at -20°C until assayed for FSH. Antiserum against inhibin used in the immunoneutralization experiment was generated using methods as described previously [29]. Antigen for anti-inhibin serum was [Tyr-30]-inhibin (1–30) conjugated to rabbit serum albumin kindly provided by Dr. N. Ling (Neurocrine Biosciences Inc., San Diego, CA).

RIAs for Inhibin, Estradiol, Progesterone, and FSH

Plasma concentrations of inhibin were measured in triplicate (50 µl per sample) using a rabbit antiserum against bovine inhibin (TNDH-1) and 125-I-labeled 32-kDa bovine inhibin as described previously [30]. Partially purified bovine follicular fluid inhibin was used for immunization in an adult castrated Japanese white rabbit. The inhibin antiserum (TNDH-1) showed no significant cross reaction with LH, FSH, or prolactin of rats, cattle, and sheep, or with GnRH, transforming growth factor, or activin, whereas the antiserum cross-reacts with inhibin Pro-{alpha} and free inhibin {alpha}-subunit [4]. The intra- and interassay coefficients of variation were 10.8% and 12.2%, respectively.

Plasma concentrations of estradiol and progesterone were determined by a double-antibody RIA system using 125I-labeled radioligands as described previously [31]. Antisera against estradiol (GDN 244) [32] and progesterone (GDN 377) [33] were kindly provided by Dr. G.D. Niswender (Animal Reproduction and Biotechnology, Colorado State University, Fort Collins, CO). The plasma estradiol was measured in duplicate (500 µl per sample), and the intra- and interassay coefficients of variation were 5.8% and 11.4%, respectively; the displacement of tracer with estradiol standards (0.3125–640.0 pg) and plasma (100–1000 µl) produced excellent dose-response curves. Plasma progesterone was measured in triplicate (50 µl per sample), and the intra- and interassay coefficients of variation were 3.5% and 13.4%, respectively.

Concentrations of plasma FSH were measured by a heterologous double-antibody RIA using an NIDDK RIA kit for rat FSH as described previously [34, 35]. Iodinated preparation was FSH-I-5, and the antiserum used was anti-rat FSH-S-11. Results were expressed in terms of NIDDK rat FSH-RP-2. The intra- and interassay coefficients of variation were 4.8% and 6.8%, respectively.

Immunohistochemistry

Ovaries were immediately removed from animals and placed in methacarn fixative (mixture of methyl alcohol, chloroform, and acetic acid: 6:3:1) at room temperature overnight. After fixation, the ovaries were dehydrated in alcohol baths, cleared in xylene, and embedded in paraffin. Sections (6 µm) were cut and mounted on slides coated with poly-L-lysine. The slides were dried for more than 24 h at 32°C, then deparaffinized with xylene and rehydrated in graded ethanol before being washed in water. To expose epitopes, sections were autoclaved for 15 min at 121°C in sodium citrate buffer (0.01 M, pH 6.0 ). The sections were incubated in 3% H2O2 methanol at 32°C for 30 min to reduce endogenous peroxidase activity and then in 0.5% casein-Tris saline (0.05 M Tris-HCl with 0.15 M NaCl, pH 7.6) at 37°C for 1 h to quench nonspecific staining. Then the sections were used for inhibin immunohistochemical staining as described previously [14]. Sections were incubated for 24–36 h at 4°C with polyclonal antibodies against inhibin subunits. The antibodies against each inhibin subunit were anti-[Tyr 30] porcine-inhibin {alpha}-chain (1–30)-NH2 conjugated to rabbit serum albumin (kindly provided by Dr. N. Ling, Neuroendocrine Inc., San Diego, CA), and anti-inhibin ßA (81–113)-NH2 (#305–24-D) and anti-ßB (80–112)-NH2 (#305–25-D) (kindly provided by Dr. W. Vale, The Salk Institute for Biological Studies, La Jolla, CA). Binding sites of antibodies were visualized by the ABC Kit Elite, and 0.05% 3,3'-diaminobenzidine tetrachloride (Sigma Chemical Co., St. Louis, MO) in 10 mM Tris-buffered saline containing 0.01% H2O2 for 1 min. Specificity of the antibodies was examined using normal rabbit serum instead of primary antibody. In order to identify the cell types within the ovary, the next serial section was stained with hematoxylin and eosin.

Statistics

All data were expressed as mean ± SEM and were analyzed by one-way ANOVA. When a significant effect was obtained with one-way ANOVA, Student's t-test or the Cochran-Cox test was used for analyzing the significance of the difference between two means in the experiment on the estrous cycle (the data of plasma FSH during estrous cycle were transformed by the logarithms), the nonparametric Friedman's test was used for analyzing the significance of effect in the ovariectomy experiment, and Duncan's multiple-range procedure was used for analyzing the immunoneutralization experiment. A value of p < 0.05 was considered to be statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Characterization of the Inhibin RIA System (Fig. 1)

Displacement of tracer with partially purified bovine inhibin, pooled peripheral plasma of intact (12.5–100 µl) and ovariectomized (12.5–100 µl) adult female guinea pigs, and ovarian homogenates of adult guinea pigs produced excellent dose-response curves. These curves were parallel with the bovine inhibin standard curve, indicating that it was possible to measure the concentration of plasma inhibin in the guinea pig using the present RIA method.



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  		FIG. 1. Dose-response curves of bovine 32-kDa inhibin (solid circles), pooled peripheral plasma of intact (squares) and ovariectomized (triangles) adult female guinea pigs, and ovarian homogenates (open circles) of adult guinea pigs in the inhibin RIA. Each value represents the mean of triplicate determinations.

Length of Estrous Cycle and Changes in the Plasma Concentrations of FSH, Inhibin, Estradiol, and Progesterone during the Estrous Cycle (Fig. 2)

The mean length (± SEM) of the 122 estrous cycles for the 85 animals studied was 16.1 ± 0.2 days with a range of 13–22 days.



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  		FIG. 2. Changes in concentrations of FSH (a), inhibin (b), estradiol (c), and progesterone (d) during the estrous cycle in guinea pigs. Each value represents the mean ± SEM of 5 animals. #p < 0.05 compared with the value of Day 0. *p < 0.05 indicates significant difference between two means (Student's t-test or Cochran-Cox test).

Plasma inhibin and estradiol increased beginning on Day 10 after ovulation (ovulation was indicated by Day 0), decreased after ovulation, and remained low during the luteal phase; there then appeared a significant elevation at about Day 9. A significant positive correlation was observed between inhibin and estradiol (r = 0.4069, n = 83) throughout the estrous cycle. Plasma FSH was low before Day 0, when inhibin and estradiol were high and progesterone was low, and then rose during the luteal phase, when both inhibin and estradiol were low and progesterone was high. Plasma concentrations of progesterone increased significantly after Day 2, remained high during the luteal phase, and then decreased significantly after Day 13.

Effects of Ovariectomy on Plasma Concentrations of Inhibin, FSH, and Progesterone (Fig. 3)

The nonparametric Friedman's test showed significant effects on plasma concentrations of inhibin (p < 0.05), FSH (p < 0.01), and progesterone (p < 0.01), respectively, after ovariectomy. The concentrations of plasma inhibin showed an abrupt decrease to 36.8% by 30 min and a further decrease to 18.6% of the initial levels by 3 h after ovariectomy. The low levels of plasma inhibin were maintained for 48 h after surgery. Plasma progesterone also decreased abruptly after ovariectomy and maintained significant low but detectable levels by 6 h. Plasma FSH had increased significantly by 12 h after ovariectomy over initial values, and these high concentrations were maintained for 48 h.



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  		FIG. 3. Effects of ovariectomy on the plasma concentrations of inhibin (a), FSH (b), and progesterone (c). Each value represents the mean ± SEM of 5 animals. The nonparametric Friedman's test showed a significant effect on plasma concentrations of inhibin (p < 0.05), FSH (p < 0.01), and progesterone (p < 0.01) after ovariectomy.

Immunohistochemistry (Figs. 4 and 5)

In a healthy large follicle (700–800 µm in diameter) before ovulation, the granulosa cell layer consisted of 7–8 layers of cells, and the theca interna was composed of large epithelioid cells. Immunohistochemically, clearly positive staining for inhibin {alpha}, ßA, and ßB subunits was observed in granulosa cells of one or two large healthy follicles in each ovary before ovulation. There was no positive reaction for inhibin {alpha}, ßA, and ßB subunits in the corpora lutea or other follicles.



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  		FIG. 4. Immunohistochemical staining of inhibin subunits in guinea pig ovary.<<004>> a) Stained with hematoxylin and eosin;<<004>> b) stained with normal rabbit serum (NRS); c, d, and e) stained with anti-inhibin {alpha}-, ßA-, ßB-subunit sera, respectively. Bar = 100 µm.



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  		FIG. 5. The same plates as in Figure 4, shown at higher magnification. a) Stained with hematoxylin and eosin; b) stained with normal rabbit serum (NRS); c, d, and e) stained with anti-inhibin {alpha}-, ßA-, ßB-subunit sera, respectively. Bar = 100 µm.

Effects of Immunoneutralization of Endogenous Inhibin on Plasma Concentrations of FSH (Fig. 6)

Injection of anti-inhibin serum to female guinea pigs that had received s.c. implants of progesterone for 23–33 days induced an elevation of plasma FSH in a dose-dependent manner. Injection of 1.0 ml anti-inhibin serum significantly increased the plasma concentrations of FSH at 6 h after the injection, and plasma FSH remained elevated until 48 h later.



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  		FIG. 6. Plasma concentrations of FSH after injection of control serum (squares) or anti-inhibin serum (0.5 ml, circles; 1.0 ml, triangles) into female guinea pigs bearing progesterone capsules. Values represent mean percentage of the initial values of each group ± SEM for 6 animals. *p < 0.05 compared with the value of controls (Duncan's multiple-range procedure).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The present study is the first to depict sequential changes in plasma inhibin and estradiol during the estrous cycle of guinea pigs. These data clearly indicate that the predominant secretion of inhibin in the circulation occurs during the follicular phase. There were two increases in plasma estradiol at Days 8–9 and Days 14–2, and two increases in plasma inhibin at Day 9 and Days 13–2; these were in agreement with the published biphasic phenomenon of ovarian follicle development in guinea pigs [2, 3, 36]. A significant positive correlation was observed between inhibin and estradiol throughout the estrous cycle, although the increase in plasma inhibin preceded that of estradiol in guinea pigs. Plasma inhibin started to increase during the early follicular phase of animals whose ovaries contained several small antral follicles, whereas plasma estradiol showed a clear increase during the late follicular phase, a few preovulatory follicles were observed in the ovaries. These results support our hypothesis that inhibin is a chemical signal of the number of growing follicles in the ovary, and that estradiol is a signal of follicular maturation in the ovary in many other mammals [37–39].

The pattern of plasma FSH during the estrous cycle of guinea pigs agreed with previous reports [18, 22, 40] and was also similar to data for cows [4, 41]. The ovariectomy experiment showed an increase in plasma FSH without ovarian inhibition in the guinea pig. This supports the hypothesis that inhibin and estradiol are the major inhibitors of FSH secretion. Anti-inhibin serum was injected into guinea pigs bearing long-term progesterone implants. The results of this injection confirmed that inhibin is an important factor in the regulation of FSH secretion during the estrous cycle in guinea pigs. These results are similar to those reported in other animals, such as rats [42], hamsters [43], cows [44], and ewes [45], in which it was shown that the passive immunoneutralization of inhibin can induce an increase in plasma concentrations of FSH.

Plasma concentrations of inhibin decreased after ovulation during the estrous cycle in guinea pigs, as in other rodents, such as rats [46] and hamsters [13]. Compared with other animals having functional luteal phases, the pattern of inhibin secretion during the estrous cycle of guinea pigs was very similar to that of cows [4]. Plasma inhibin decreased abruptly after ovariectomy; this confirmed that the ovary was the main source of inhibin secretion in guinea pigs. But plasma inhibin remained detectable after ovariectomy (Figs. 1 and 3), perhaps because of inhibin Pro-{alpha} and free inhibin {alpha}-subunit from other sources, as seen in other animals [47–51].

The immunohistochemistry experiments showed that inhibin may be secreted mainly from the granulosa cells of one or two healthy large follicles in the ovary before ovulation in guinea pigs. It is reported that the expression of the inhibin/activin subunits ({alpha}, ßA, ßB) mRNAs and proteins varies with follicular maturity in the rat [52–54] and human [55]; and within the ovary, inhibin/activin exert both autocrine and paracrine functions in the modulation of gonadotropin-mediated follicular development [7, 56–59]. The present result showing inhibin/activin subunits ({alpha}, ßA, ßB) indicates that the same immunolocalization in granulosa cells of one or two healthy large follicles before ovulation is found in guinea pigs, suggesting that the inhibin/activin exerts both autocrine and paracrine functions in the modulation of follicular development and selection of dominant follicles. However, guinea pigs show staining characteristics for inhibin {alpha} subunit that are different from those from rats [54] and hamsters [13], in which the granulosa cells of all follicles stained. This disparity may be due to the different ovulation rates in each species.

The pattern of estradiol secretion during the estrous cycle of guinea pigs appears to be largely similar to that observed in other species having functional luteal phases, such as cows, sheep, and pigs [60]. The plasma concentrations of progesterone during the estrous cycle show changes typical in other animals; i.e., they are high during the luteal phase and low during the follicular phase [18–21]. It is thus confirmed that the plasma concentrations of progesterone can be used as an index of luteal function in guinea pigs.

In conclusion, the present study demonstrates that inhibin is mainly secreted by granulosa cells of one or two healthy large follicles in the ovary, and it plays an important role in the regulation of FSH secretion during the estrous cycle in the guinea pig.


   ACKNOWLEDGMENTS
 
We wish to express our gratitude to the National Hormone and Pituitary Program, Rockville, MD, for providing RIA materials for rat FSH; to Dr. G.D. Niswender, Animal Reproduction and Biotechnology, Colorado State University, Fort Collins, CO, for providing antisera to progesterone (GDN 337) and estradiol (GDN 244); to Dr. N. Ling, Neurocrine Inc., San Diego, CA, for providing [Tyr30]-inhibin (1–30); to Dr. W. Vale, The Salk Institute for Biological Studies, La Jolla, CA, for providing anti-cyclic inhibin ßA (81–113) (#305–24-D) and anti-cyclic inhibin ßB (80–112) (#305–25-D); and to Teikoku Hormone, MFG Co. Ltd, Tokyo, Japan, for providing progesterone and estradiol.


   FOOTNOTES
 
1 This work was supported in part by a grant-in-aid (Monbusho International Scientific Research Program: Joint Research) from the Ministry of Education of Japan. Back

2 Correspondence: Kazuyoshi Taya, Laboratory of Veterinary Physiology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. FAX: 81 42 367 5767; taya{at}cc.tuat.ac.jp Back

Accepted: August 17, 1998.

Received: April 21, 1998.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Sutherland SD, Festing MFW. The guinea-pig. In: Trevor BP (ed.), The UFAW Handbook on the Care and Management of Laboratory Animals. 6th edition. Avon: The Bath Press, Langman Scientific and Technical; 1987: 393–410.
  2. Bland KP. Biphasic follicular growth in the guinea-pig oestrous cycle. J Reprod Fertil 1980; 60:73–76.[Abstract]
  3. Hutz RJ, Bejvan SM, Durning M, Dierschke DJ. Changes in follicular populations in serum estrogen and progesterone, and in ovarian steroid secretion in vitro during the guinea-pig estrous cycle. Biol Reprod 1990; 42:266–276.[Abstract]
  4. Kaneko H, Watanabe G, Taya K, Sasamoto S, Hasegawa Y. Changes in plasma concentrations of immunoreactive inhibin, estradiol and FSH during the follicular waves during the estrous cycle of cows. J Reprod Dev 1995; 41:311–320.[CrossRef]
  5. Brand A, deJong WHR. Qualitative and quantitative micromorphological investigations of the tertiary follicle population during the estrous cycle in sheep. J Reprod Fertil 1973; 33:431–439.[Medline]
  6. Quandt LM, Hutz RJ. Induction by estradiol-17ß of polycystic ovaries in the guinea pig. Biol Reprod 1993; 48:1088–1094.[Abstract]
  7. Vale W, Hsueh A, Rivier C, Yu J. The inhibin/activin family of hormones and growth factor. In: Sporn MB, Robert AB (eds.), Handbook of Experimental Pharmacology. Heidelberg: Springer-Verlag; 1990: 95:211–248.
  8. Mason AJ, Niall HD, Seeberg PH. Structure of two human ovarian inhibin. Biochem Biophy Res Commun 1986; 35:957–964.
  9. Esch FS, Shimasaki S, Cooksey K. Complementary deoxyribonucleic acid (cDNA) cloning and DNA sequence analysis of rat ovarian inhibins. Mol Endocrinol 1987; 1:388–396.[Abstract]
  10. Depaolo LV, Shander D, Wise PM, Barraclough CA, Channing CP. Identification of inhibin-like activity in ovarian venous plasma of rats during the estrous cycle. Endocrinology 1979; 105:647–657.[Medline]
  11. Kimura J, Katoh M, Taya K, Sasamoto S. An inverse relationship between inhibin and follicle-stimulating hormone during the period of ovulation induced by human chorionic gonadotrophin in diestrous rats. J Endocrinol 1983; 97:313–318.[Abstract]
  12. Tsukamoto I, Taya K, Watanabe G, Sasamoto S. Inhibin activity and secretion of gonadotropin during the period of follicular maturation. Life Sci 1986; 39:119–125.[CrossRef][Medline]
  13. Kishi H, Taya K, Watanabe G, Sasamoto S. Follicular dynamics and secretion of inhibin and oestradiol-17ß during the oestrous cycle of the hamster. J Endocrinol 1995; 146:169–176.[Abstract]
  14. Otsuka M, Kishi H, Arai K, Watanabe G, Taya K, Greenwald GS. Temporal Changes in inhibin, steroid hormones, and steroidogenic enzymes during induced follicular atresia in the hypophysectomized cyclic hamster. Biol Reprod 1997; 56:423–429.[Abstract]
  15. Yamoto M, Minami S, Nakano R, Kobayash M. Immunohistochemical localization of inhibin/activin subunits in human ovarian follicles during the menstrual cycle. J Clin Endocrinol Metab 1992; 74:989–993.[Abstract]
  16. Yamoto M, Minami S, Nakano R. Immunohistochemical localization of inhibin subunits in human corpora lutea during the menstrual cycle. J Clin Endocrinol Metab 1991; 73:470–477.[Abstract]
  17. Yamoto M, Minami S, Nakano R. Immunohistochemical localization of inhibin subunits in polycystic ovary. J Clin Endocrinol Metab 1993; 77:859–862.[Abstract]
  18. Challis JRG, Heap RB, Illingworth DV. Concentrations of oestrogen and progesterone in the plasma of nonpregnant, pregnant and lactating guinea-pigs. J Endocrinol 1971; 51:333.[Medline]
  19. Donovan BT, Lockhart AN. Gonadal hormones and the control of ovulation in the guinea pig. J Endocrinol 1972; 55:599–607.[Medline]
  20. Blatchley FR, Donovan BT, Terhaar MB. Plasma progesterone and gonadotrophin levels during estrous cycle of the guinea pig. Biol Reprod 1976; 15:29–38.[Abstract]
  21. Heap RB, Perry JS, Rowland IW. Corpus luteum function in the guinea-pig: arterial and luteal progesterone levels, and the effects of hysterectomy and hypophysectomy. J Reprod Fertil 1967; 13:537–553.[Medline]
  22. Croix D, Franchimont P. Changes in the serum levels of the gonadotrophins, progesterone and estradiol during the estrous cycle of the guinea pig. Neuroendocrinology 1975; 19:1–11.[Medline]
  23. Garris DR, Foreman D. Follicular growth and atresia during the last half of luteal phase of the guinea pig estrous cycle; relation to serum progesterone and estradiol levels and utero-ovarian blood flow. Endocrinology 1984; 115:73–77.[Abstract]
  24. Westfahl PK, Verasy MS. Changes in serum and ovarian steroids during reproductive development in the female guinea pig. Biol Reprod 1988; 39:1086–1092.[Abstract]
  25. Joshi HS, Watson DJ, Labhsetwar AP. Ovarian secretion of oestradiol, oestrone, 20-dihydroprogesterone and progesterone during the oestrous cycle of the guinea-pig. J Reprod Fertil 1973; 35:177–181.[Medline]
  26. Norris ML, Adams CE. The vaginal smear, mating, egg transport and preimplantation development in a wild guinea-pig, the cuis (Galea musteloides). J Reprod Fertil 1979; 55:457–461.[Abstract]
  27. Lu JK, Judd HL. Silastic implants of progesterone produce high circulating levels of both progesterone and 20{alpha}-hydroxyprogesterone in ovariectomized, adrenalectomized rats. Biol Reprod 1982; 26:385–390.[Abstract]
  28. Ueda H, Kosaka T, Takahashi KW. Effects of long-term progesterone treatment on synchronized ovulation in guinea pigs. Zool Sci 1988; 5:139–143.
  29. Taya K, Sasamoto S. Mechanisms responsible for suppression of FSH and LH during lactation in the rat. J Endocrinol 1991; 129:119–130.[Abstract]
  30. Hamada T, Watanabe G, Kokuho T, Taya K, Sasamoto S, Hasegawa Y, Miyamoto K, Igarashi M. Radioimmunoassay of inhibin in various mammals. J Endocrinol 1989; 122:697–704.[Abstract]
  31. Taya K, Watanabe G, Sasamoto S. Radioimmunoassay for progesterone, testosterone and estradiol-17ß using 125-I-iodohistamine radioligands. Jpn J Anim Reprod 1985; 31:186–197.
  32. Korenman SG, Steven RH, Carpenter LA, Robb M, Niswender GD, Sherman BM. Estradiol radioimmunoassay without chromatography: procedure, validation and normal value. J Clin Endocrinol Metab 1974; 38:718–720.[Medline]
  33. Gibori G, Anrczak E, Rothchild I. The role of estrogen in regulation of luteal progesterone secretion in the rat after day 12 of pregnancy. Endocrinology 1977; 100:1483–1495.[Abstract]
  34. Bast JD, Green GS. Serum profiles of follicle-stimulating hormone, luteinizing hormone and prolactin during the estrous cycle of the hamster. Endocrinology 1974; 94:1295–1299.[Medline]
  35. Donovan BT, Terhaar MB, Lockhart AN, Peddie MJ. Changes in the concentration of follicle-stimulating hormone in plasma during development in the guinea-pig. J Endocrinol 1975; 64:521–528.[Abstract]
  36. Hermreck AS, Greenwald GS. The effects of unilateral ovariectomy on follicular maturation in the guinea pig. Anat Rec 1964; 148:171–176.[CrossRef][Medline]
  37. Taya K. Roles of inhibin in regulation of FSH secretion and folliculogenesis in mammals. Curr Trends Exp Endocrinol 1993; 1:97–116.
  38. Taya K, Kaneko H, Takedomi T, Kishi H, Watanabe G. Role of inhibin in regulation of FSH secretion and folliculogenesis in cows. Anim Reprod Sci 1996; 42:563–570.[CrossRef]
  39. Taya K, Kaneko H, Watanabe G, Sasamoto S. Inhibin, and secretion of FSH in oestrous cycle of cows and pigs. J Reprod Fertil Suppl 1991; 43:151–162.[Medline]
  40. Donovan BT, Terhaar MB, Lockhart AN, Peddie MJ. Changes in the concentration of follicle-stimulating hormone in plasma during development in the guinea-pig. J Endocrinol 1975; 64:521–528.
  41. Roche JF. Control and regulation of folliculogenesis—a symposium in perspective. Rev Reprod 1996; 1:19–27.[Abstract]
  42. Arai K, Watanabe G, Taya K, Sasamoto S. Role of inhibin and estradiol in the regulation of FSH and LH secretion during the estrous cycle of the rat. Biol Reprod 1996; 55:127–133.[Abstract]
  43. Kishi H, Okada T, Otsuka M, Watanabe G, Taya K, Sasamoto S. Induction of superovulation by immunoneutralization of endogenous inhibin through the secretion of FSH in cyclic golden hamster. J Endocrinol 1996; 151:65–75.[Abstract]
  44. Kaneko H, Nakanishi Y, Taya K, Kishi H, Watanabe G, Sasamoto S, Hasegawa Y. Evidence that inhibin is an important factor in the regulation of FSH secretion during the mid-luteal phase in cows. J Endocrinol 1993; 136:35–41.[Abstract]
  45. Mann GE, Campbell BK, McNeilly AS, Baird DT. Passively immunizing ewes against inhibin during the luteal phase of the oestrous cycle raises the plasma concentration of FSH. J Endocrinol 1989; 123:383–391.[Abstract]
  46. Watanabe G, Taya K, Sasamoto S. Dynamics of ovarian inhibin secretion during estrous cycle of the rat. J Endocrinol 1990; 126:151–157.[Abstract]
  47. Depaolo LV, Shimonaka M, Ling N. Regulation of pulsatile gonadotropin secretion by estrogen, inhibin, and follistatin (activin-binding protein) in ovariectomized rats. Biol Reprod 1992; 46:898–904.[Abstract]
  48. King BF, Britt JH, Esbenshade KL, Flowers WL, Ireland JJ. Evidence for a local role of inhibin on inhibin alpha subunits in compensatory ovarian hypertrophy. J Reprod Fertil 1995; 104:291–295.[Abstract]
  49. Klein R, Findley JK, Clarke IJ, de Kretser DM, Robertson DM. Radioimmunoassay of FSH-suppressing protein in the ewe: concentrations during the oestrous cycle and following ovariectomy. J Endocrinol 1993; 137:433–443.[Abstract]
  50. Mcasey ME, Machen N, Benson B. Immunoreactive inhibin decreases following bilateral ovariectomy and during the postovulatory rise of FSH in Syrian hamsters. Life Sci 1995; 57:2057–2071.[CrossRef][Medline]
  51. Peeters R, Vanmontfort D, Van Isterdael J, Verhoeven G, Rombauts L, Decuypere E. Evidence for the presence of immunoreactive inhibin in extragonadal tissues of ovariectomized ewes. Anim Reprod Sci 1997; 48:257–268.[CrossRef][Medline]
  52. Woodruff TK, D'Agostino J, Schwartz NB, Mayo KE. Dynamic changes in inhibin messenger RNAs in rat ovarian follicles during the reproductive cycle. Science 1988; 239:1296–1299.[Abstract/Free Full Text]
  53. Turner IM, Saunders PTK, Shimasaki S, Hillier SG. Regulation of inhibin subunit gene expression by FSH and estradiol in cultured rat granulosa cells. Endocrinology 1989; 125:2790–2792.[Abstract]
  54. Meunier H, Cajander SB, Roberts VJ, Rivier C, Sawchenko PE, Hsueh AJW, Vale W. Rapid changes in the expression of inhibin {alpha}-, ßA-, ßB-subunits in ovarian cell types during the rat estrous cycle. Mol Endocrinol 1988; 2:1352–1363.[Abstract]
  55. Veronica JR, Sara B, Albert ER. Expression of inhibin/activin subunits and follistatin messenger ribonucleic acids and proteins in ovarian follicles and the corpus luteum during the human menstrual cycle. J Clin Endocrinol Metab 1993; 77:1402–1410.[Abstract]
  56. Mather JP, Woodruff TK, Krummen LA. Paracrine regulation of reproductive function by inhibin and activin. Soc Exp Biol Med 1992; 201:1–15.[Medline]
  57. Woodruff TK, Lyon RJ, Hansen SE, Rice GC, Mather JP. Inhibin and activin locally regulate rat ovarian folliculogenesis. Endocrinology 1990; 127:3196–3205.[Abstract]
  58. De Jong FH. Inhibin. Physiol Rev 1988; 68:555–607.[Abstract/Free Full Text]
  59. Findlay JK. An update on the roles of inhibin, activin, and folliculogenesis. Biol Reprod 1993; 48:15–23.[Abstract]
  60. Hansel W, Concannon PW, Lukaszewska JH. Corpora lutea of the large domestic animal. Biol Reprod 1973; 8:222–245.



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