The influence of estradiol-17beta and progesterone on peripheral serum concentrations of luteinizing hormone and follicle stimulating hormone in the ovariectomized ewe

Serum gonadotropin concentrations were high and variable and fluctuated episodically in short and long term ovariectomized ewes. Treatment with solid silastic implants releasing progesterone (serum levels 1.81 +/- 0.16 ng/ml) had no consistent effect. Treatment with implants releasing estradiol-17beta significantly depressed mean serum gonadotropin concentrations and peak height to values usually seen in intact ewes. This occurred regardless of implant size and serum estradiol-17beta concentrations (range 11 +/- 0.3 pg/ml to 98 +/- 12.8 pg/ml). Progesterone and estradiol-17beta together significantly depressed the frequency of peaks in LH concentration. Following progesterone removal, 95% of the ewes treated with progesterone and estradiol-17beta implants experienced a transient increase in serum LH concentrations similar to the preovulatory surge in intact ewes. Eighty-four percent of the LH surges were accompanied by a surge in serum FSH concentrations. However, following progesterone removal, 5.1 +/- 2.1 FSH surges were observed over six days. Gonadotropin surges occurred regardless of estradiol-17beta implant size and with or without the influence of supplemental estradiol-17beta.     

Serum and urinary levels of reproductive hormones associated with the estrous cycle in white-tailed deer (Odocoileus virginianus)

Concentrations of estradiol-17β (E₂), progesterone (P_o), and luteinizing hormone (LH) in serum and estrone glucuronide (E₁G) and pregnanediol glucuronide (PdG) in urine were determined by direct radioimmunoassay in five yearling and three adult female white-tailed deer (Odocoileus virginianus) from 14 October to 20 December 1985. Elevated levels of LH were recorded before the first estrus of the breeding season and immediately preceding or during behavioral estrus. Urinary E₁G and PdG concentrations were poorly correlated with serum levels of E₂ and P_o, respectively. Serum P_o levels prior to the first estrus of the breeding season indicate that pubertal yearlings experience silent ovulations and suggest that silent ovulations may be important in the transition from adolescence to cycling adult in white-tailed deer. © 1992 Wiley-Liss, Inc.     

Effects of intracerebroventricular administration of irisin on the hypothalamus–pituitary–gonadal axis in male rats

Irisin is a product of fibronectin type III domain-containing protein 5 (FNDC5) and plays an important role in energy homeostasis. In this study, we aimed to determine effects of intracerebroventricular administration of irisin on the hypothalamus–pituitary–gonadal axis by molecular, biochemical, and morphological findings. Fourty male Wistar-Albino rats were used and divided into four groups including control, sham (vehicle), 10, and 100 nM irisin infused groups (n = 10). Hypothalamic gonadotropin releasing hormone (GnRH) level and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined. Testicular tissue histology and spermiogram analysis were also performed. Both irisin concentrations significantly reduced hypothalamic GnRH messenger RNA (mRNA) and protein levels (p < 0.05). It was found that serum LH, FSH, and testosterone levels and Sertoli and Leydig cell numbers were decreased by irisin administration (p < 0.05). In addition, irisin administration reduced sperm density and mobility (p < 0.05). However, it did not cause any change in testicular and epididymis weights and tubular diameter. Our results reveal that irisin can play a role in the central regulation of reproductive behavior and also reduces testosterone levels by suppressing LH and FSH secretion. These results suggest that the discovery of irisin receptor antagonists may be beneficial in the treatment of infertility.     

Influence of synthetic lamprey GnRH-III on gonadotropin release and steroid hormone levels in gilts

Based on the supposition that lamprey GnRH-III (lGnRH-III) elicits FSH releasing activity in swine, synthetic lGnRH-III (peforelin, Maprelin® XP10) was used in puberal estrus synchronized gilts. The secretion of reproductive hormones FSH, LH, estradiol and progesterone was analyzed, and follicle growth and ovulation recorded. Altogether, 24 German Landrace gilts were treated after an 18-day long synchronization of the estrus cycle with Regumate® as follows: 48 h after the last Regumate® feeding they received im either 150 μg Maprelin® XP10 (lGnRH-III, group Maprelin, n = 6), 50 μg Gonavet Veyx® (GnRH-I agonist, group GnRH, n = 6), 850 IE Pregmagon® (eCG, group eCG, n = 6) or saline (group Control, n = 6). Additionally, in eight gilts the concentrations of FSH and LH were analyzed after treatment with 150 μg Maprelin® XP10 (n = 3), 50 μg Gonavet Veyx® (n = 3) or saline (n = 2) at mid-cycle (day 10 of the estrus cycle). Blood samples were collected via implanted jugular vein catheters. Ovarian features were judged endoscopically at the end of the Regumate® feeding and on days 5 and 6 after treatment. Maprelin® XP10 had no effect on FSH release in gilts; neither at the pre-ovulatory period or at mid-cycle. Furthermore, LH levels were unaffected. In contrast, GnRH-I agonist stimulates FSH release, however less compared to LH secretion. LH secretion was induced by GnRH-I both during the follicular phase and at mid-cycle. Equine CG did not stimulate the release of pituitary hormones FSH and LH due to its direct action on the ovary. Increased estradiol concentrations during days 2 to 5 after Regumate® in all treatment groups indicated pre-ovulatory follicle growth in gilts. Equine CG stimulated a higher (P < 0.01) number of ovulatory follicles compared to the other treatment groups. All together, 83 to 100 % of gilts ovulated by day 6 post treatment. In summary, results of our study on reproductive hormone secretion do not provide evidence that synthetic lGnRH-III (Maprelin® XP10) selectively releases FSH in estrus synchronized gilts.     

Validation of radioimmunoassays for LH and FSH in the sooty mangabey (Cercocebus atys): Characterization of LH and the response to GnRH

Heterologous radioimmunoassays (RIA) for macaque LH and FSH were validated for the measurement of these hormones in the sooty mangabey and mangabey pituitary LH was characterized relative to rhesus monkey LH. Dilutions of a pituitary mangabey extract and a partially purified preparation of mangabey LH ran parallel to a rhesus monkey standard (LER 1909-2) in the ovine-ovine (o-o) LH assay but showed some deviation from parallelism in the rhesus monkey FSH assay. The LH potency of the mangabey extract and standard were six and 190 times more potent, respectively, than LER 1909-2 in the LH RIA. Mangabey LH was estimated to have a molecular weight of 40,000–42,000 daltons vs 35,000–38,000 daltons for rhesus LH on Sephadex G-100 chromatography. Plasma levels of radioimmunoreactive LH, FSH, and testosterone were assayed before and after a bolus administration of 25, 50, or 100 μg synthetic go-nadotropin releasing hormone (GnRH) to adult male mangabeys. A significant increase in serum levels of LH was seen within 30 min with levels more than fourfold higher than the basal level of LH after administration of 100 μg GnRH. However, no consistent increases in plasma FSH values were detected. The integrated mean LH response above preinjection levels following 25, 50, or 100 μg GnRH was dose related. Serum levels of testosterone were also elevated after administration of GnRH, but peak concentrations of testosterone lagged behind peak levels of LH by approximately 30 min. These studies indicate that the heterologous RIAs may be used for measuring gonadotropins in the mangabey and that the male mangabey is apparently more sensitive to GnRH than the rhesus monkey.     

Regulation of gonadotropin secretion and puberty onset by neuromedin U

Neuromedin U (NMU), an anorexigenic peptide, was originally isolated from porcine spinal cord in 1985. As NMU is abundant in the anterior pituitary gland, we investigated the effects of NMU on gonadotropin secretion. Both NMU and its receptors, NMUR1 and NMUR2, were expressed in the pituitary gland. NMU suppressed LH and FSH releases from rat anterior pituitary cells. Moreover, NMU-deficient mice exhibit an early onset of vaginal opening. The LHbeta/FSHbeta ratio, which is an index of puberty onset, is high in young NMU-deficient mice. These results indicate that NMU suppresses gonadotropin secretion and regulates the onset of puberty.     

Excitatory amino acids as modulators of gonadotropin secretion

Summary The effects of quinolinic acid (QUIN) and quisqualate (QA) on the secretion of GnRH from MBH and LH and FSH from AP of 50 day old male rats have been evaluated by means of an in vitro perifusion technique.QUIN (100µM) is able to increase GnRH secretion with an action mediated by an NMDA receptor type, as shown by the inhibitory effect exerted by both a competitive (AP-5) and a non-competitive (MK-801) specific antagonist.QA per se at the concentrations tested (1–100µM) does not modify GnRH and gonadotropin secretion, but in the presence of a specific KA/QA receptor antagonist (DNQX) exerts a stimulatory effect at both levels.This observation might indicate that of the two QA receptor subtypes (ionotropic and metabotropic), this agonist binds to the metabotropic one with very low affinity: thus it is likely that a higher dose is required in order to have any effect on gonadotropin secretion. However, in the presence of DNQX, which binds to the ionotropic receptor, all the available QA can bind to the metabotropic one and can exert its action at MBH AP levels.     

Insights into male germ cell apoptosis due to depletion of gonadotropins caused by GnRH antagonists

The role of pituitary gonadotropins in the regulation of spermatogenesis has been unequivocally demonstrated, although, the precise mechanism of this regulation is not clearly understood. Previous studies have shown that specific immunoneutralization of LH/testosterone caused apoptotic cell death of meiotic and post-meiotic germ cells while that of FSH resulted in similar death of meiotic cells. In the present study, the death process of germ cells has been characterized by depleting both FSH and testosterone by administering two different potent GnRH antagonists, Cetrorelix and Acyline to both rats and mice. Pro-survival factors like Bcl-2 and Bcl-x/l were unaltered in germ cells due to GnRH antagonist treatment, although a significant increase in several pro-apoptotic markers including Fas and Bax were evident at both protein and RNA levels. This culminated in cytochrome C release from mitochondria and eventually increase in the activity of caspase-8 and caspase-3. These data suggest that both extrinsic and intrinsic apoptotic death pathways are operative in the germ cells death following decrease in FSH and testosterone levels. Multiple injections of GnRH antagonist resulted in complete disappearance of germ cells except the spermatogonial cells and discontinuation of the treatment resulted in full recovery of spermatogenesis. In conclusion our present data suggest that the principal role of FSH and testosterone is to maintain spermatogenic homeostasis by inhibiting death signals for the germ cells.     

转铁蛋白抑制大鼠卵泡颗粒细胞FSH受体的结合与维持

转铁蛋白能抑制大鼠卵泡颗粒细胞的分化,但其机理尚不清楚。本实验用已烯雌酚处理后分离的大鼠颗粒细胞,观察了转铁蛋白对FSH结合到颗粒细胞,以及在培养过程中对颗粒细胞FSH受体量维持的影响。结果表明,生理浓度范围的转铁蛋白部分地阻断了~(125)I-rFSH结合到颗粒细胞上;将转铁蛋白与FSH一起处理细胞,发现它能剂量依赖性地抑制FSH对颗粒细胞FSH受体的维持作用,并表现为孕酮及雌二醇的分泌减少。     

Antiprogestagen RU486 prevents the LH-dependent decrease in the serum concentrations of inhibin in the rat

Summary 1. In the rat, the LH-dependent ovarian progesterone rise mediates several actions of the primary surge of LH on the ovary. This experiment was aimed at elucidating the effects of the antiprogestagen RU486 on the LH-dependent decrease in both the serum concentrations and the ovarian content of inhibin.2. All rats in this experiment were treated with an antagonist of LHRH (1 mg/200 µl saline at 0800 h in proestrus) to supress the endogenous release of LH. One group of rats received 32 µg LH/250 µl saline at 1200 h in proestrus. Other group was given 4 mg RU486/200 µl oil at 0800 h in proestrus. The third group was injected with both RU486 and LH. Rats from the control group were injected with 250 µl saline and 200 µl oil. Animals were decapitated at 1700 h in proestrus and trunk blood and ovaries collected to determine the serum concentrations of LH, FSH, progesterone, 17ß-estradiol and inhibin as well as the ovarian content of inhibin.3. The ovulatory dose of LH in LHRHa-treated rats decreased both the serum concentrations and the ovarian content of inhibin and increased the serum concentrations of FSH. The administration of RU486 blocked the effect of LH on the serum concentrations of inhibin but not that on the ovarian content of inhibin.4. Since the antiprogestagen RU486 blocked the effect of LH on the serum concentrations of inhibin, we conclude that ovarian progesterone, besides mediating the effects of the primary LH surge on the ovulatory process and luteinization, participates in the LH-dependent drop in the serum concentrations of inhibin in proestrous afternoon.     

Effect of FSH and HCG on progesterone secretion by cultured oocyte-cumulus complexes and granulosa cells from porcine antral follicles: Influence of follicular development

Oocyte-cumulus complexes and granulosa cells were harvested from small (1–2 mm), medium (3–5 mm), and large (6–12 mm) porcine antral follicles and cultured for 2 and 3 days. The effects of various doses of purified hCG and human FSH on progesterone secretion and monolayer formation were examined. After a 2-day culture period it was found that FSH was more effective in stimulation of progesterone secretion by cultured oocyte-cumulus complexes than in granulosa cells harvested from small follicles (P < 0.01), whereas hCG was more effective in stimulating progesterone secretion in granulosa cells than in oocytecumulus complexes harvested from large follicles. In contrast, after a 3-day culture period, granulosa cells secreted more progesterone compared to oocytecumulus complexes under control conditions or in the presence of hCG or FSH. After 3 days both FSH and hCG stimulated progesterone secretion by oocytecumulus complexes and granulosa cells; however, the hormone effect was greater upon granulosa cells than oocyte-cumulus complexes. After 3 days of culture in the case of both follicular cell types, there was a greater response to FSH in the case of cells harvested from small compared to large follicles. The reverse was true in the case of hCG responsiveness. Monolayer formation ability of oocyte-cumulus complexes was greater in the case of complexes harvested from small and medium than complexes harvested from large follicles. Addition of hCG to the cultures led to a dose-dependent decrease in monolayer formation by oocyte-cumulus complexes harvested from all sizes of follicles.     

多疣狭口蛙皮肤分泌物中FSH和LH的分离及在不同繁殖期的表达

运用聚丙烯酰胺凝胶电泳、葡聚糖凝胶层析、酶联免疫等实验方法,对多疣狭口蛙Kaloula verrucosa繁殖前期、繁殖期、繁殖后期的皮肤分泌物进行初步的成分分离,并对其不同时期皮肤分泌物成分中卵泡刺激素(Follicle stimulating hormone,FSH)及黄体生成素(Luteinizing hormone, LH)进行了免疫检测和定量比较.结果 表明:多疣狭口蛙皮肤分泌物中FSH的含量在其繁殖前期处于三个时期中的最高,繁殖期次之,繁殖后期最低;而LH则是在繁殖期含量最高,繁殖前期含量略偏低,到繁殖后期含量最低.     

GnRH脉冲模式对FSH分泌的影响

本文目的是进行GnRH脉冲模式对FSH分泌影响的研究。用GnRH以不同的脉冲振幅、不同的频率对GTH细胞进行刺激后,检测FSH的24 h分泌量。结果表明,FSH的24 h分泌量,以频率为120 min、振幅20 nmol/L时的GnRH脉冲模式为最高,并且随着GnRH刺激频率的增快或减慢,FSH的分泌量均呈逐渐减少趋势。所以,GnRH脉冲频率本身就是一个调控信号,不同脉冲频率GnRH对FSH表达有着明显不同的影响,在相同振幅条件下,低频脉冲刺激(120 min间隔)时FSH的分泌达到高峰。