Follicle stmulating hormone ( FSH ) consist of alpha and beta subunits, which are encoded by se-parate genes. Pituitary release of FSH appears to be regulated by the hypothalamic GnRH and the gonadal steroid hormones. In addition, inhibin and follistatin produced by the gonad have been known to inhibit FSH secretion selectively. However, little is known about their regulation of the biosynthesis of FSH subunits at transcriptional and posttranscriptional levels. In the pre-sent study, we studied the time course of changes in alpha and FSH beta subunit mRNA concentrati-ons after castration and the effects of ovarian steroids of changes in alpha and FSH beta subunit mRNA concentrations after castration and the effects of ovarian steroids on alpha and FSH beta subunit mRNA in ovariectomized rats in order to determine Whether FSH subunit synthesis is modulated at the pretranslational levels, and whether synthesis and secretion are differently regulated. Results are as follows : 1. The time course of the rise in the steady state alpha subunit and FSH beta subunit mRNA levels were observed after ovariectomy, which paralleled the increases in serum and pituitary FSH concentrations. The time course experiments revealed differences in the patterns of alpha and FSH beta subunit mRNA responses, the rise in FSH beta subunit mRNA levels being more pro- minent than the rise in alpha subunit mRNA. 2. FSH beta mRNA levels were negatively regulated by the single injection of progesterone but not by estradiol, suggesting that FSH beta subunit mRNA seemed to be more sensitive to ne-gative feedback by progesterone than estradiol. Similar results were obtained by the continuous treatment of ovarian steroids for 1~4 days, but inhibition was more prominent with continuous treatment. It is, therefore, concluded that estradiol and progesterone inhibit the synthesis of FSH at the pretranslational level by modulating the steady state levels of alpha and FSH beta subunit mRNA, progesterone effect being more promiment than that of estradiol and alpha and FSH beta subunit are regulated in a different manner.
Animals ; Castration ; Estradiol ; Female ; Follicle Stimulating Hormone* ; Follicle Stimulating Hormone, beta Subunit ; Follistatin ; Gonadal Steroid Hormones ; Gonadotropin-Releasing Hormone ; Gonads ; Inhibins ; Ovariectomy* ; Progesterone ; Rats* ; RNA, Messenger* ; Steroids

OBJECTIVESTo measure continuously the urine beta-FSH excretion in the patients with male hypogonadism, and to evaluate the significance of urine beta-FSH when used in the clinical practice and pathophysiological study on male hypogonadism.

METHODSFour health male volunteers (aged 19, 22, 27 and 33 years), four patients with the hypogonadotropic hypogonadism (aged 17, 17, 19 and 24 years) and five patients with idiopathy hypogonadism (hypergonadotropic, aged 16, 16, 17, 20 and 22 years) were asked to collect their morning-first urine samples for 30 to 32 days. One normal men collected his urine samples for 63 days. The urine beta-FSH was assayed with the method of EIA, then corrected by creatinine (Cr) concentration.

RESULTSThe urine beta-FSH level of normal men was (1.16 +/- 0.20) micrograms/mg Cr, with the peak variation in their curves, peak level at 2.76 micrograms/mg Cr. The levels of urine beta-FSH of 4 patients with the hypogonadotropic hypogonadism were lower significantly than those of normal men [(0.58 +/- 0.31) (0.93 +/- 0.47) (0.47 +/- 0.33) and (0.60 +/- 0.40) micrograms/mg Cr], without fluctuation in their curves. beta-FSH levels of 5 patients with idiopathy hypogonadism were higher significantly [(3.02 +/- 0.93), (4.36 +/- 1.12), (4.79 +/- 0.78), (4.64 +/- 1.42) and (3.88 +/- 1.42) micrograms/mg Cr], with irregular fluctuation, the highest peak level at 6.83 micrograms/mg Cr. The second sexual characteristics of hypogonadal patients were poor and serum testosterone levels low.

CONCLUSIONSThe urine beta-FSH level raised with irregular fluctuation in patients with idiopathy hypogonadism, while lowed without any fluctuation in patients with the hypogonadism. These findings suggested that the urine beta-FSH excretion was useful for the clinically classified diagnoses and pathophysiological study on male hypogonadism, and for observing the treatment reaction of androgen replacement.

Adolescent ; Adult ; Follicle Stimulating Hormone, beta Subunit ; urine ; Humans ; Hypogonadism ; metabolism ; urine ; Luteinizing Hormone ; urine ; Male ; Testosterone ; urine

OBJECTIVE: To compare the effectiveness and convenience of a pen device for the self-administration of follitropin beta with a conventional syringe delivering follitropin beta solution in patients undergoing IVF-ET. METHODS: GnRH agonist long protocol was used for controlled ovarian stimulation (COS) in all subjects. A total of 100 patients were randomized into the pen device group or the conventional syringe group on the first day of COS. Local tolerance reactions were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On the day of hCG injection, patients were asked to rate their overall pain and convenience experienced with self-injection on a visual anlaogue scale (VAS). RESULTS: There were no differences in patients' characteristics between the two groups. The duration of COS was significantly shorter in the pen device group than in the conventional syringe group. Patients included in the pen device group needed a significantly smaller amount of follitropin beta. However, no differences between the two groups were found in IVF results and pregnancy outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours after the injection was significantly lower in the pen device group. VAS scores indicated that injections using the pen device were significantly less painful and more convenient. CONCLUSION: The pen device for self-administration of follitropin beta is less painful, safer and more convenient for the patients, and can be more effective because of the shorter duration and smaller dose of follitropin beta when compared with the conventional syringe.
Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Follicle Stimulating Hormone, beta Subunit ; Follicle Stimulating Hormone, Human ; Gonadotropin-Releasing Hormone ; Humans ; Incidence ; Injections, Subcutaneous ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Recombinant Proteins ; Syringes

OBJECTIVE: To compare the effectiveness and convenience of a pen device for the self-administration of follitropin beta with a conventional syringe delivering follitropin beta solution in patients undergoing IVF-ET. METHODS: GnRH agonist long protocol was used for controlled ovarian stimulation (COS) in all subjects. A total of 100 patients were randomized into the pen device group or the conventional syringe group on the first day of COS. Local tolerance reactions were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On the day of hCG injection, patients were asked to rate their overall pain and convenience experienced with self-injection on a visual anlaogue scale (VAS). RESULTS: There were no differences in patients' characteristics between the two groups. The duration of COS was significantly shorter in the pen device group than in the conventional syringe group. Patients included in the pen device group needed a significantly smaller amount of follitropin beta. However, no differences between the two groups were found in IVF results and pregnancy outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours after the injection was significantly lower in the pen device group. VAS scores indicated that injections using the pen device were significantly less painful and more convenient. CONCLUSION: The pen device for self-administration of follitropin beta is less painful, safer and more convenient for the patients, and can be more effective because of the shorter duration and smaller dose of follitropin beta when compared with the conventional syringe.
Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Follicle Stimulating Hormone, beta Subunit ; Follicle Stimulating Hormone, Human ; Gonadotropin-Releasing Hormone ; Humans ; Incidence ; Injections, Subcutaneous ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Recombinant Proteins ; Syringes

BACKGROUND: FSH is a heterodimeric glycoprotein and is composed of alpha and beta subunits. alpha subunit is common to FSH and LH, while an unique beta subunit determines the biological specificity of each hormone. The synthesis of beta subunit is the primary rate-limiting step in the synthesis of each hormone. Although FSH plays a pivotal role in folliculogenesis and ovulation, very little studies have been performed on the regulation of FSH beta gene expression. Therefore, the present study attempted to examine the effect of GnRH or activin on the expression of FSH beta mRNA as well as FSH release and signaling pathway involved in their actions. METHODS: The primary cultures of rat anterior pituitary were used for this study. To determine FSH beta mRNA levels, northern blotting method was used. The concentration of FSH in the culture medium was evaluated by using a specific radioimmunoassay for rat FSH. RESULTS: PMA, an activator of PKC, increased FSH beta mRNA levels and FSH release, whereas forskolin, an activator of adenylate cyclase, showed no effect. The application of GnRH augmented FSH release, but not FSH beta mRNA levels. However, the administration of activin increased FSH beta mRNA levels as well as FSH release. Staurosporine, an inhibitor of PKC, suppressed activin-induced increment of FSH beta mRNA levels and FSH release. CONCLUSION: The present study demonstrated that activin rather than GnRH is a major regulator for FSH beta mRNA expression, and suggest that PKC-dependent pathway is also involved in the action of activin on the expression of FSH beta mRNA and FSH release.
Activins ; Adenylyl Cyclases ; Animals ; Blotting, Northern ; Colforsin ; Female ; Follicle Stimulating Hormone ; Follicle Stimulating Hormone, beta Subunit ; Gene Expression* ; Glycoproteins ; Gonadotropin-Releasing Hormone ; Ovulation ; Radioimmunoassay ; Rats* ; RNA, Messenger ; Sensitivity and Specificity ; Staurosporine

ObjectiveTo study the relationship of the single nucleotide polymorphisms (SNP) rs34349826 (c.104 A>G) and rs6521 (c.114 C>G) of the luteinizing hormone beta-subunit (LHB) gene with male infertility in Chinese men.

METHODSThis case-control study included 405 males with primary infertility (the infertility group) and 424 normal fertile men (the control group), the former again divided into subgroups of oligospermia, severe oligozoospermia and azoospermia according to the sperm concentration. Clinical data were collected from all the subjects and genomic DNA obtained from their peripheral blood for genotyping rs34349826 and rs6521 of the LHB gene by Sequence MassArray. We analyzed the correlation of male infertility with the SNPs of the two loci using the logistic regression model as well as its association with their haplotype combination with the SHEsis online software.

RESULTSThere were statistically significant differences between the control and infertility groups in the semen volume (［3.51 ± 1.36］ vs ［3.74 ± 1.71］ ml, P <0.05), sperm concentration (［79.21 ± 61.60］ vs ［27.37 ± 30.80］ ×10⁶/ml, P <0.01), percentage of progressively motile sperm (［39.40 ± 9.64］ % vs ［11.90 ± 14.72］ %, P <0.01), and levels of serum luteinizing hormone (LH) (［3.29 ± 1.39］ vs ［6.25 ± 4.83］ IU/L, P <0.01) and follicle-stimulating hormone (FSH) (［4.56 ± 2.31］ vs ［15.64 ± 17.03］ IU/L, P <0.01). Logistic regression analysis revealed no correlation between male infertility and the genotypes of the rs34349826 and rs6521 loci of the LHB gene, and similar results were found in the subgroups of the infertile males. SHEsis analysis on the haplotypes of the rs34349826 and rs6521 loci showed the GG genotype combination to be a protective factor against male infertility.

CONCLUSIONSThe rs34349826 and rs6521 loci of the LHB gene were not related to male infertility, which can be further confirmed by larger-sample studies. The GG genotype combination is a protective factor against male infertility.

Adult ; Azoospermia ; genetics ; Case-Control Studies ; China ; Follicle Stimulating Hormone ; Genotype ; Haplotypes ; Humans ; Infertility, Male ; genetics ; Logistic Models ; Luteinizing Hormone ; Luteinizing Hormone, beta Subunit ; genetics ; Male ; Oligospermia ; genetics ; Polymorphism, Single Nucleotide ; Sperm Count