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PubMed1990

Varying dose-response characteristics of different immunoassays and an in-vitro bioassay for FSH are responsible for changing ratios of biologically active to immunologically active FSH.

Serum FSH levels in fertile and infertile men were determined by applying the Sertoli cell in-vitro bioassay and six different immunoassays. Bioassay and immunoassay estimates were significantly correlated (r ranging from 0.78 to 0.86; P less than 0.01). On average, all immunoassays measured lower FSH concentrations in samples with low FSH levels and higher FSH concentrations in those with high FSH levels compared with the bioassay. Ratios of bioactivity to immunoreactivity (B/I) were highest in fertile men and lowest in men with severe disturbances of testicular function. Depending on which immunoassay was used these differences were either significant or only marginal. Dose-response characteristics for WHO FSH standard preparation 78/549, used in the bioassay as well as in the immunoassays, were different between immunoassays and the bioassay, suggesting that decreasing B/I ratios with increasing FSH serum levels were method-related and reflected different slopes of the dose-response characteristics of the assays, rather than being true changes in the molecular composition of FSH. The present investigation underlines the necessity of choosing the immunoassay used for comparison with the bioassay carefully and of validating the system in regard to parallelism between dose-response characteristics. B/I ratios must be interpreted with great caution and previous studies which report changing B/I ratios in various endocrine situations may have to be reevaluated.

Biological Assay↗
PubMed1989

Follicle stimulating hormone (FSH) induces G protein dissociation from FSH receptor-G protein complexes in reconstituted proteoliposomes.

We have previously reported incorporation of Triton X-100-solubilized bovine calf testis membrane protein into liposomes. The resulting proteoliposomes responded to FSH by exchange of bound GDP for [3H]5'-guanylyl imidodiphosphate ([3H]Gpp(NH)p) and by activation of adenylate cyclase (AC) (Grasso, P., Dattatreyamurty, B. and Reichert, L.E., Jr. (1988) Mol. Endocrinol. 2, 420-430). This model system was utilized to study the effects of FSH on the quaternary structure of FSH receptor-associated GTP-binding protein by comparing the gel filtration profiles of proteoliposomes solubilized with Triton X-100 after exposure to [3H]Gpp(NH)p in the presence or absence of FSH. FSH caused a redistribution of radioactivity (due to bound [3H]Gpp(NH)p) from a high molecular weight fraction (Mr greater than 100,000) to a fraction of much lower molecular weight (Mr approximately 23,000). These results are interpreted to reflect an FSH-induced dissociation of [3H]Gpp(NH)p-bound G protein from its receptor-associated complex. The apparent Mr of approximately 23,000 for the FSH receptor-associated GTP-binding protein suggests that it may represent yet another member of a family of low molecular weight GTP-binding proteins, possibly a ras gene product, recently identified in various mammalian tissues.

Animals↗
PubMed1993

Developmental changes of testicular activin and FSH receptor mRNA and plasma FSH and inhibin levels in the rat.

To investigate the changes in the FSH receptor and the activin receptor during sexual maturation in rat testes, we examined the mRNA levels of the receptors by Northern blot analysis. With a full length rat activin receptor cRNA probe in this study, Northern blot analysis revealed two activin receptor mRNAs (6Kb and 3Kb) in testes. The large messenger (6Kb) was low on day 7, and gradually increased by day 35. On the other hand, the small messenger (3Kb) was low on day 7, began to increase on day 21, and had increased dramatically by day 35. Therefore, compared with our previous data, developmental changes in the mRNA of the activin receptor of male and female gonads showed certain differences. The expression of 3Kb activin receptor mRNA in rat testis may be relevant to the stimulated spermatogenesis in this period. 2.4Kb and 5.5Kb FSH receptor mRNA were revealed on day 7 and decreased to 80% on day 14 and remained at the same level. The Scatchard plots of FSH binding data showed that the binding affinities of testicular FSH were constant at each stage of development. Changes in the mRNA level in FSH receptor were followed by changes in the concentration of FSH receptor in testis. The rise in the plasma FSH level was concomitant with the decrease in the plasma inhibin level by day 14.

Activin Receptors↗
PubMed2000

Mutations in the follicle-stimulating hormone-beta (FSH beta) and FSH receptor genes in mice and humans.

Follicle-stimulating hormone (FSH), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex steroids and gametes. FSH-beta (FSH beta) and FSH receptor (FSHR) knockout mice display impaired ovarian follicular development and infertility in females and small testes, oligospermia, and fertility in males. Humans with FSH beta gene mutations tend to have a more severe phenotype than those with FSHR gene mutations, although infertility and varying degrees of impaired sex steroid production occur in both types of mutations. Data from human and mouse mutations in the FSH beta and FSHR genes suggest that FSH is necessary for normal pubertal development and fertility in males and females.

Animals↗
PubMed2003

Postendocytotic trafficking of the follicle-stimulating hormone (FSH)-FSH receptor complex.

Although the fates of the internalized hormone-receptor complexes formed by the lutropin/choriogonadotropin and the TSH receptors have been examined in some detail, much less is known about the fate of the internalized FSH-FSH receptor (FSHR) complex. Using biochemical and imaging approaches we show here that the majority of the internalized FSH-FSHR complex accumulates in endosomes and subsequently recycles back to the cell surface where the bound, intact hormone dissociates back into the medium. Only small amounts of FSH and the FSHR are routed to a lysosomal degradation pathway, and the extent of FSH-induced down-regulation of the cell surface and total FSHR is minimal. This pathway was detected in heterologous (human kidney 293T) cells transfected with the rat (r) or human (h) FSHR as well as in a mouse Sertoli cell line (MSC-1) or a mouse granulosa cell line (KK-1) transfected with the rFSHR.Additional experiments using a series of C-terminal deletions of the rFSHR and the hFSHR showed that the recycling of the internalized FSH-FSHR complex and the extent of hFSH-induced down-regulation is dictated by a short stretch of amino acids present at the extreme C-terminal end of the receptor.We conclude that most of the internalized FSH-FSHR complex is recycled back to the cell surface, that this recycling pathway is highly dependent on amino acid residues present near the C terminus of the FSHR, and that it is an important determinant of the extent of down-regulation of the FSHR.

Amino Acid Sequence↗
PubMed1998

Levels of messenger RNA encoding ovarian receptors for FSH and LH in cattle during superovulation with equine chorionic gonadotrophin versus FSH.

This study tested the hypothesis that luteal LH receptor (LHr) and follicular LHr and FSH receptor (FSHr) steady-state mRNA levels are greater during superovulation with equine chorionic gonadotrophin (eCG) compared with that with FSH. Heifers were stimulated with eCG (n = 10) or FSH (n = 10), and ovaries were recovered the day before and at 12 and 24 h after luteolysis was induced with prostaglandin F2 alpha (PGF2 alpha). Total RNA was purified from individual follicles and corpora lutea. Steady-state levels of LHr and FSHr mRNA were assessed by slot blot analysis employing homologous cDNA probes. There were no differences in luteal LHr between FSH- and eCG-stimulated animals before luteolysis, and hybridization signals were detected in only one of six animals by 12 h after injection of PGF2 alpha. After PGF2 alpha injection, steady-state levels of follicular LHr were 4-fold lower (P < 0.05) and follicular FSHr mRNA levels were 2.4-fold lower (P < 0.05) in eCG- compared with FSH-treated cattle. In eCG-treated animals, induction of luteolysis led to a significant increase in follicular LHr mRNA levels (P < 0.01) and a significant decrease in follicular FSHr mRNA levels (P < 0.01). There was no such effect of luteolysis in FSH-treated animals. We conclude that superovulation with eCG, compared with FSH, results in lower follicular levels of LHr and FSHr mRNA but does not affect luteal LHr mRNA levels.

Animals↗
PubMed2001

Recombinant FSH versus urinary gonadotrophins or recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: Over the last four decades, various urinary FSH (uFSH) products of different purity have been developed. In 1988 recombinant FSH (rFSH ) was prepared by transfecting Chinese hamster ovary cell lines with both FSH subunit genes. Both rFSH and uFSH are known to be effective in inducing ovulation in women with clomiphene-resistant polycystic ovary syndrome. Ovulation induction with FSH bears the risk of multiple follicle development, multiple pregnancies and ovarian hyperstimulation syndrome. The dose regimen used can affect the incidence of these complications. OBJECTIVES: To compare in women with clomiphene-resistant polycystic ovary syndrome (PCOS) the safety and effectiveness in terms of ovulation, pregnancy, miscarriage, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) of 1) rFSH with uFSH and 2) different dose regimens of rFSH. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. SELECTION CRITERIA: All relevant published RCT's were selected. Randomised controlled trials were eligible for inclusion if treatment consisted of recombinant FSH versus urinary FSH or recombinant FSH in different dose regimens, to induce ovulation in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. Handsearching of bibliographies of relevant publications and reviews and abstracts of scientific meetings was performed. Serono Benelux BV and NV Organon, the manufacturers of follitropin alpha (Gonal F(R)) and follitropin beta (Puregon(R)) respectively, were asked for unpublished data and ongoing studies. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed according to predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Four randomised trials comparing rFSH versus uFSH were identified. No significant differences were demonstrated for the relevant outcomes. The odds ratio for ovulation rate was 1.19 (95% CI 0.78,1.80), for pregnancy rate 0.95 (95% CI 0.64,1.41), for miscarriage rate 1.26 (95% CI 0.59,2.70), for multiple pregnancy rate 0.44 (95% CI 0.16,1.21) and for OHSS 1.55 (95% CI 0.50,4.84). Similarly, in the only randomised trial that compared chronic low dose versus conventional regimen with rFSH no significant differences were found. REVIEWER'S CONCLUSIONS: At this moment there are not sufficient data to determine which of rFSH or uFSH is preferable for ovulation induction in women with PCOS.

Clomiphene↗
PubMed1994

In vitro Sertoli cell bioassay of follicle-stimulating hormone (FSH)-serum from different animal species alters the morphology of rat Sertoli cells without affecting their response to FSH.

Follicle-stimulating hormone (FSH) stimulates aromatase activity of immature rat Sertoli cells cultured in vitro in the presence of an androgen substrate, a phenomenon that can be used to measure FSH bioactivity. This paper analyzes the effects of sera from various animal species on both aromatase activity and morphological aspects of cultured rat Sertoli cells. Treatment of Sertoli cells with increasing concentrations of serum from humans, monkeys, rats, hamsters, and mice gave a dose-dependent stimulation of estradiol production parallel to the response obtained with FSH standard. Serum from these species and from rabbits also had a characteristic morphological effect on the cells, to produce a fibroblast-like aspect and clumping. This effect was dose-dependent, was increased by the addition of FSH, and was eliminated by heating the sera at 56 degrees for 30 min prior to incubation with the cells. Clumping did not interfere with the aromatase activity of Sertoli cells and did not cause the cellular response to deviate from parallelism with the standard curve. Heat treatment of FSH standard and serum samples did not significantly change the aromatase activity. FSH bioactivity could be measured accurately in intact and castrated monkeys. It is concluded that the Sertoli cell aromatase bioassay can be applied directly to the measurement of serum bioactive FSH in several animal species without any preliminary treatment of the serum samples.

Animals↗
PubMed2001

Clinical experience with recombinant follicle-stimulating hormone (FSH) and urinary FSH: a retrospective case- controlled analysis.

OBJECTIVE: To compare the efficacy and efficiency of recombinant FSH (rFSH) and urinary FSH (uFSH). DESIGN: Retrospective case controlled analysis. SETTING: An assisted reproduction unit at a university center. PATIENT(S): 1388 patients undergoing long protocol in vitro fertilization/embryo transfer (IVF-ET) using buserelin acetate from day 2 of the cycle and either rFSH (follitropin beta) (n = 694) or uFSH (n = 694) with equal number of ampules started (rFSH: 50 IU, uFSH: 75 IU). INTERVENTION(S): Patients were included in the two groups of treatment after matching for similarity in age and type of treatment (IVF or intracytoplasmic sperm injection). MAIN OUTCOME MEASURE(S): Total dose of FSH, ovarian response, and IVF outcome. RESULT(S): Patients who received uFSH experienced a shorter period of stimulation, and a higher number of oocytes were collected. The total FSH used was lower in the rFSH group, and they required a lower FSH dose per oocyte retrieved. The implantation and pregnancy rates were similar between the uFSH and rFSH groups. In both groups implantation and pregnancy rates were higher when intracytoplasmic sperm injection was performed as compared with IVF. CONCLUSION(S): The implantation and pregnancy rates are similar when either rFSH or uFSH is used (when compared on an ampule-to-ampule basis, rFSH: 50 IU, and uFSH: 75 IU). However, a significantly lower total FSH dose was used in the rFSH group with a lower FSH dose per oocyte collected.

Adult↗
PubMed1996

An elevated day three follicle-stimulating hormone:luteinizing hormone ratio (FSH:LH) in the presence of a normal day 3 FSH predicts a poor response to controlled ovarian hyperstimulation.

OBJECTIVE: To determine if an elevated FSH:LH ratio predicts response in infertile patients undergoing controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Retrospective study. SETTING: The Division of Reproductive Endocrinology at the Mount Sinai Medical Center, New York, New York. PARTICIPANTS: Seventy-four patients undergoing IVF-ET using similar protocols for COH with day 3 FSH, LH, and E2 testing available for analysis. All patients were < 41 years of age and had day 3 serum FSH < 15 mIU/mL (conversion to SI unit, 1.00). MAIN OUTCOME MEASURES: Follicle-stimulating hormone:LH ratio, day 8 serum E2, peak serum E2, cancellation rate, pregnancy rate, and number and size of follicles. RESULTS: An FSH:LH ratio > or = 3.6 (group I) predicted a poor response to COH (sensitivity 85.7% and specificity 95%). There were no significant differences regarding day 3 serum FSH and ampules of gonadotropins used for COH. Group I (ratio > or = 3.6) patients responded to COH with lower day 8 E2 (97 +/- 18 versus 319 +/- 36 pg/mL; conversion factor to SI unit, 3.671), peak E2 (422 +/- 115 versus 2,368 +/- 183 pg/mL), and fewer follicles > 15 mm (1.3 +/- 0.5 versus 17.1 +/- 1.0). In group I the cycle cancellation rate (12/14) was significantly higher than the group II cycle cancellation rate (2/60) and pregnancy rate in group II (ratio < 3.6) was 25%. CONCLUSIONS: The FSH:LH ratio may increase before a dramatic increase in serum FSH is observed and appears to be a useful marker of ovarian reserve.

Adult↗
PubMed2003

Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3.

Follicle-stimulating hormone (FSH) comprises an alpha subunit and a beta subunit, whereas the FSH receptor consists of two halves with distinct functions: the N-terminal extracellular exodomain and C-terminal membrane-associated endodomain. FSH initially binds to exodomain, and the resulting FSH/exodomain complex modulates the endodomain and generates signal. However, it has been difficult to determine which subunit of FSH contacts the exodomain or endodomain and in what orientation FSH interacts with them. To address these crucial issues, the receptor was Ala-scanned and the hormone subunits were probed with photoaffinity labeling with receptor peptides corresponding to the N-terminal region of the exodomain and exoloop 3 of the endodomain. Our results show that both regions of the receptors are important for hormone binding and signal generation. In addition, the FSH beta subunit is specifically labeled with the N-terminal peptide, whereas the alpha subunit is labeled with the exoloop 3 peptide. These contrasting results show that the FSH beta subunit is close to the N-terminal region and that the alpha subunit is projected toward exoloop 3 in the endodomain. The results raise the fundamental question whether the alpha subunit, common among the glycoprotein hormones, plays a major role in generating the hormone signal common to all glycoprotein hormones.

Amino Acid Sequence↗
PubMed2002

The role of LH and FSH in ovarian androgen secretion and ovarian follicular development: clinical studies in a patient with isolated FSH deficiency and multicystic ovaries.

Inactivating mutations have proven to be instructive in elucidating the role of FSH in human ovarian function. We performed a detailed reproductive endocrine evaluation of a patient with inactivating mutations in the FSH beta-subunit gene who was hypo-estrogenic and had LH excess. The patient underwent a pelvic ultrasound and overnight frequent blood sampling followed by a human chorionic gonadotrophin (HCG) stimulation test. One month later she received human recombinant FSH, followed 24 h later by a second HCG stimulation test. Despite a mean LH serum concentration and LH pulse characteristics typical for polycystic ovaries (PCOS), baseline and dexamethasone-suppressed free testosterone were low-normal. The administration of HCG led to minimal stimulation of 17-hydroxyprogesterone and androgens. The patient had multicystic ovaries containing follicles 3-5 mm in diameter and responded to FSH with prompt increases in estradiol and inhibin B. There were no clinical or laboratory consequences of LH excess in this FSH-deficient woman. These findings support the hypothesis that excessive LH stimulation alone does not cause ovarian hyperandrogenism. We also found that follicular development was present in the absence of FSH. These antral follicles had apparently developed normally, since estradiol and inhibin B increased promptly after FSH administration.

17-alpha-Hydroxyprogesterone↗
PubMed2002

From HMG through purified urinary FSH preparations to recombinant FSH: a substitution study.

Drugs produced through the use of recombinant DNA techniques have become an integral part of medical practice. Before recombinant FSH (rFSH) was introduced in 1996, FSH purified from the urine of postmenopausal women had been commercially available since the 1960s. We analysed the diffusion and the substitution patterns of the different FSH preparations in The Netherlands. The fact that rFSH preparations have batch-to-batch consistency, are free from urinary protein contaminants and have the potential to be produced in limitless quantities, is advantageous. The question whether newer, more pure FSH products are beneficial from the clinical perspective, has not been settled beyond reasonable doubt. The price of rFSH is three times as high as the price of the former FSH preparations. Due to the introduction of rFSH, total FSH expenditures have grown from 5.0 million Euros in 1995, to 26.8 million Euros in 2000, while the volume increased by <100%. Both the pharmaceutical companies and purchasers (government, insurers) have influenced the patterns of substitution of existing FSH products by biotech equivalents. In general, the risk of increasing pharmaceutical costs without clear clinical benefits has to be set against the risk of strangling innovations. Therefore, a continuous process of technology assessment is necessary.

Biotechnology↗
PubMed2002

Single dose pharmacokinetics and effects on follicular growth and serum hormones of a long-acting recombinant FSH preparation (FSH-CTP) in healthy pituitary-suppressed females.

BACKGROUND: A long-acting FSH preparation has been developed by site-directed mutagenesis and gene transfer techniques. METHODS: In this open-label trial, we investigated the pharmacokinetic and pharmacodynamic properties of FSH-CTP (corifollitropin alpha, Org 36286) in healthy female volunteers. Twenty-four subjects were treated with a high-dose oral contraceptive (OC) to suppress pituitary function. A single dose of 15, 30 or 60 micro g FSH-CTP was injected (s.c., eight subjects per dose group) and seven of these 24 subjects were subsequently treated with a single dose of 120 micro g. RESULTS: Maximum serum FSH-CTP concentrations (0.42, 0.66, 1.49 and 3.27 ng/ml after administration of 15, 30, 60 and 120 micro g Org 36286 respectively) were reached between 36 and 48 h after injection and t(1/2) varied between 60 and 75 h. Dose proportionality was shown across the studied dose range, whereas t(max) and t(1/2) were dose independent. In most subjects follicular growth was observed; the number and maximum diameter of the follicles increased with the dose. Follicles with a diameter vertical line 8.0 mm were observed only in the 60 and 120 micro g dose groups, diameters between 12.0 and 15.9 mm occurred only in the 120 micro g group. Serum LH and 17beta-oestradiol levels remained low due to profound pituitary suppression whereas inhibin-B levels increased with dose. Maximum mean inhibin-B levels were 30.4, 322.7 and 1059.3 pg/ml in the 30, 60 and 120 micro g dose group respectively. The preparation was safe and well tolerated, and no FSH-CTP antibody formation was observed. CONCLUSIONS: The pharmacokinetics of FSH-CTP were shown to be proportional with the dose. The elimination half-life was approximately two times longer than that of rFSH. A single dose of FSH-CTP was shown to be safe and able to induce multiple follicular growth accompanied by a dose-dependent rise in serum inhibin-B concentrations.

Adult↗
PubMed2000

Insulin-like growth factor I increases follicle-stimulating hormone (FSH) content and gonadotropin-releasing hormone-stimulated FSH release from coho salmon pituitary cells in vitro.

The effects of insulin-like growth factor I (IGF-I) and insulin on the function of coho salmon gonadotropes in vitro were investigated. Dispersed pituitary cells from immature coho salmon (Oncorhynchus kisutch) were incubated with IGF-I for 1, 3, 7, or 10 days, then incubated with salmon GnRH for an additional 24 h. Medium FSH content before and after GnRH treatment and intracellular FSH content after GnRH treatment were measured. Incubation of pituitary cells with IGF-I for 7 or 10 days increased GnRH-stimulated FSH release and remaining cell content, but did not affect basal release. To examine the specificity of the effects of IGF-I, we compared FSH release and cell content of FSH and LH after 10-day incubation with a range of concentrations of IGF-I or insulin. Incubation with physiological concentrations of IGF-I resulted in significantly higher GnRH-stimulated FSH release and remaining cell content of FSH and LH. Conversely, supraphysiological concentrations of insulin were required to produce more moderate effects on gonadotropin levels. These results suggest that elevation of gonadotropin levels by IGF-I may be one mechanism by which somatic growth and nutrition promote pubertal development in salmon.

Animals↗
PubMed1992

Further evidence for differential regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH): increased FSH and decreased LH levels in a patient with familial pure gonadal dysgenesis.

There is experimental evidence that a portion of follicle-stimulating hormone (FSH) secretion is independent of hypothalamic influences. A 29 year old woman with familial pure gonadal dysgenesis developed myelodysplastic syndrome. Endocrine investigations showed discrepancy between serum FSH and luteinizing hormone (LH) levels. FSH levels remained elevated while LH levels decreased. The FSH to LH ratio was 10 (normal 2-2.5). The fall in LH is likely to be due to factor(s) involved directly and specifically in LH synthesis and release. Exogenous LH releasing hormone administration as well as hormonal replacement treatment increased LH levels. The FSH to LH ratio decreased to 7. This case supports the hypothesis of differential regulation of FSH and LH, and that FSH secretion is at least partly autonomous.

Adult↗
PubMed1986

Ovarian responses in macaques to pulsatile infusion of follicle-stimulating hormone (FSH) and luteinizing hormone: increased sensitivity of the maturing follicle to FSH.

This study investigated the relationship between plasma gonadotropin concentrations and the initiation and maintenance of preovulatory follicular growth in macaques. Eight adult cynomolgus monkeys were treated with a GnRH antagonist [AcD2Nal1-4ClDPhe2, DTrp3, DArg6, DAla10]GnRH X HOAc to block endogenous gonadotropin secretion. In four animals, a pulsatile infusion of human FSH and human LH (hLH) (one 3-min pulse/h) was initiated, and the amount of hFSH delivered per pulse was increased every 3-4 days until serum estradiol concentrations rose. Thereafter, the amount of FSH delivered per pulse was reduced by 12.5%/day for 5 days, whereas the amount of LH delivered per pulse was not altered. Results indicated that plasma FSH concentrations in the range of 15-20 mIU/ml were associated with the initiation of estrogen production; in addition, a progressive reduction in plasma FSH concentration to 8-10 mI/ml over the subsequent 5 days was accompanied by continued rises in estradiol concentrations and preovulatory follicular growth. In contrast, in four control animals, maintenance of plasma FSH concentrations at 8-10 mIU/ml for 13 days did not result in elevation in serum estradiol concentrations or antral follicular growth. These observations demonstrate that after stimulation by elevated FSH concentration, follicles can continue to mature in the presence of FSH concentrations which are unable to support the growth of less mature follicles. Thus, this may account for the mechanisms by which the maturing follicle continues to develop during the mid-through late follicular phase of the menstrual cycle, whereas other less mature follicles undergo atresia.

Animals↗
PubMed1993

Human chorionic gonadotropin or human recombinant follicle-stimulating hormone (FSH)-induced ovulation and subsequent fertilization and early embryo development in hypophysectomized FSH-primed mice.

Adult hypophysectomized FSH-primed mice were used to study ovulation, fertilization, and preimplantation embryo development. Twelve days after hypophysectomy, animals were injected sc with oFSH (4 micrograms/day) twice a day for 3 days. This resulted in large preovulatory follicles that did not secrete estrogen. Concurrent with the last FSH injection, either hCG (5 IU) or human recombinant FSH (10 IU) was injected sc to induce ovulation. Animals were mated or not and killed 1-4 days later. The ovulation rate was similar for both the hCG-induced group (FH) and the FSH-induced group (FF), 97% and 90%, respectively. About 45% of the FH mice mated successfully with 56% of the eggs fertilized compared to only 25% of the FF mice with 45% of the eggs fertilized. However, only 5% of ovulated eggs developed to four-cell stages in vivo by day 3 for the FH animals and none in the FF group. To determine the reasons for the in vivo retarded embryo development, embryos at the one- or two-cell stage were collected on day 2 from the FH group. After 96 h of culture, 22% of two-cell embryos were converted to blastocysts, and 11% of one-cell eggs divided to the four-cell stage. In contrast, 80% of two-cell embryos from normal mice develop into blastocysts by 72 h of culture. The ovarian incubation medium and serum were used to measure progesterone (P4), androstenedione (A), and estradiol (E2). The patterns of serum and in vitro production of steroids were parallel. In FH mice, P4 increased immediately on the day after hCG injection (day 1) and decreased progressively on days 2 and 3; A and E2 levels increased on day 2, A decreased on day 3, and E2 decreased on day 4. When human recombinant FSH was used to induce ovulation, there were no significant changes in serum P4 and A; E2 levels were about 4 times higher on day 1 than in the FSH-primed control, then dropped to baseline levels on days 2 and 3. However, on day 3 in both the FH and FF groups, FSH receptors were still present on the granulosa cells of antral follicles, and LH/hCG receptors were present on the granulosa cells of large antral follicles and newly formed corpora lutea.(ABSTRACT TRUNCATED AT 400 WORDS)

Androstenedione↗