The differing responsiveness of the anterior- and the middle-anterior hypothalamic area to estradiol benzoate implant: inhibition of compensatory ovarian hypertrophy.

Estradiol benzoate (E2) was chronically implanted, unilaterally or bilaterally, for about 30 days in the anterior (A-AHA) or the middle (M-AHA) portion of the anterior hypothalamic area (AHA) of unilaterally ovariectomized (ULO) and intact cyclic rats. E2 unilaterally implanted in the A-AHA partially blocked and bilaterally implanted totally blocked compensatory ovarian hypertrophy (COH) in response to ULO. E2 implanted in the M-AHA induced ovarian atrophy in ULO rats. In M-AHA E2 implanted rats, ovulation was completely inhibited, vaginal smears became persistently cornified, serum FSH was drastically suppressed to 23-24% of the estrous level, LH was unremarkably changed. These effects were less pronounced when the implant was place in the A-AHA, i.e., ovulation was partially blocked only with bilateral implantation, vaginal cycles were irregular, serum FSH was suppressed to 66% and 44% of the estrous level after unilateral and bilateral implantation, respectively, LH was rather unchanged. Uteri were neither atrophic whether the implants was placed in the A-AHA or in the M-AHA. In normal cyclic rats, the effects of E2 implantation in the two areas were similar to those observed in ULO rats, except that the effects were evident even after unilateral implantation since the brain had not been compensated. The results allowed to indicate a functional subdivision of the ventral AHA, at least into the A-AHA and the M-AHA. The M-AHA was experimentally elucidated to be more estrogen sensitive than the A-AHA for monitoring of serum FSH, and was suggested to be involved in the episodic secretion of FSH. The inhibitory effect of estrogen on COH may primarily be mediated through the M-AHA and secondarily through the A-AHA.     

Long-term caffeine-induced inhibition of EAC cell progression in relation to gonadal hormonal status

Inhibitory action of caffeine (a tri-methylxanthine alkaloid) on progression or pathogenesis of lung, breast and ovarian cancer including Ehrlich ascites carcinoma (EAC) cell development has been reported. This information led the authors to study the effect of long-term administration of caffeine (20 mg/kg/day; po for 22-27 consecutive days) on the development of EAC cells in relation to serum gonadal hormones (LH, FSH, 17-OH-beta-estradiol (E2) and progesterone) in adult Swiss albino female mice. Measurement of gonadal hormones in serum using RIA showed that (a) long-term caffeine treatment significantly increased LH (except for 27 consecutive days) and decreased FSH (except for 24 and 27 consecutive days) and both E2 and progesterone (except for 22 and 24 consecutive days) levels, (b) development of EAC cell for 10-15 days, significantly increased LH but decreased FSH, E2 and progesterone levels and (c) long-term caffeine consumption during the development of EAC cell (i) restored the EAC cell- or caffeine-induced induction of LH and reduction of FSH level to their normal levels and (ii) withdrew/reduced the EAC cell-induced reduction in only E2 but not progesterone level. These results therefore, suggest that prolonged caffeine exposures may inhibit the development of EAC cell through the reduction or restoration of EAC cell-induced disruption of ovarian hormonal status to their normal status via the modulation of Hypothalamic-Pituitary-Gonadal (HPG) axis.     

The peripubertal golden hamster and the transition between daily and estrous cycle hormone rhythms

Transitional patterns of LH, FSH, and progesterone (P4) in the circulation were studied in peripubertal female golden hamsters. A daily rhythm, with afternoon surges of these hormones, is typical of the immature female, whereas 4-day rhythms characterize the estrous cycle of the adult. Blood samples were collected repeatedly from maturing individuals at either 1400 or 1700 h. Each animal was examined daily for the appearance of regular vaginal estrous cycles as indicated by a mucous exudate on the morning of ovulation. Between Days -10 and -5 relative to first vaginal estrus (FVE), afternoon surges of LH, FSH, and P4 were often observed. From Days -5 to -1 relative to FVE, afternoon surges of LH and FSH were less frequent, but P4 retained the daily rhythmicity until Day -2. A 4-day pattern of LH secretion, but not of FSH or P4, was established prior to FVE. To determine whether or not ovulations were occurring prior to the appearance of external vaginal estrous cycles, reproductive tracts were collected from 26-34 days of age and examined for evidence of ovulation. Of 124 females, concordance between the record of daily vaginal examinations and the examinations of the ovaries and oviducts was found in 103 cases (83%). The development of ovarian follicles was correlated with FVE in peripubertal hamsters by unilateral ovariectomy. Antral follicles were found only in the last 3 days prior to vaginal estrus.     

优思悦对多囊卵巢综合征模型大鼠卵巢功能的影响及其机制研究

摘要 目的：探讨优思悦对硫酸脱氢表雄酮（dehydroepiandrosterone,DHEA）诱导的多囊卵巢综合征模型大鼠体内性激素：睾酮( testosterone,T)、雌二醇( estradiol,E2 )、促黄体生成素( luteinizing hormone,LH)及卵泡刺激素( follicle－stimulating hormone,FSH)及PI3K /AKT信号通路的的影响。方法：将60只雌性SD大鼠随机均分为3组,包括空白组、模型组及治疗组。空白组每日颈部皮下注射0.2 mL大豆油,其余各组每日颈部皮下注射DHEA 60 mg/kg+0.2 mL大豆油,持续注射35 d。造模第21 d时,每日上午制备大鼠阴道涂片,将其放置在显微镜下观察,根据细胞形态判定大鼠的动情周期,无动情周期规律视为造模成功。造模第36 d时,连续4 w对大鼠进行灌胃,每天一次。检测大鼠阴道分泌物的细胞形态、大鼠卵巢中卵泡发育的情况。放射免疫法测定大鼠血清中T、E2、LH、FSH的含量;RT-qPCR法检测大鼠卵巢组织中PI3K /AKT信号通路相关因子（IＲS-1、AKT-2、CSK-3β、GLUT-4 mRNA和PTEN mRNA）的表达变化。结果：空白组大鼠的动情周期有规律性,而模型组大鼠的动情周期失去规律性,且模型组大鼠卵巢中的卵泡呈囊状扩张,血清中T、LH水平明显升高（P<0.05）,同时卵巢组织中的IRS-1、AKT-2、CSK-3β、GLUT-4 mRNA表达减少（P<0.05）,PTEN mRNA表达增多（P<0.05）。与模型组比较,优思悦可改善PCOS模型大鼠动情周期,降低血清T、LH水平（P<0.05）,改善卵泡发育,减少囊状扩张卵泡的形成,上调IRS-1、AKT-2、CSK-3β、GLUT-4 mRNA表达量,下调PTEN mRNA 表达量。结论：优思悦可有效治疗DHEA诱导的PCOS模型大鼠,与卵巢中的PI3K /AKT信号通路相关因子的基因表达相关。     

Divergent regulation of gonadotropin subunit mRNA levels by androgens in the female rat.

To examine the effects of gonadal steroids on the pretranslational regulation of the gonadotropin subunits in the female, adult female rats, beginning 7 or 28 days after ovariectomy, received daily injections of testosterone propionate (T), dihydrotestosterone propionate (D), or estradiol benzoate (E) for 7 days. Intact cycling females and ovariectomized rats that received vehicle served as controls. Serum was obtained for LH and FSH levels to assess changes in gonadotropin secretion. Total RNA from individual rats was recovered and analyzed by blot hybridization with specific radiolabeled cDNA probes for the alpha, LH beta, and FSH beta subunits. Autoradiographic bands were quantitated and standardized to mRNA levels in the intact animals. Ovariectomy resulted in a rise in serum gonadotropin levels and all three gonadotropin subunit mRNA levels. Estrogen replacement resulted in suppression of alpha, LH beta, and FSH beta mRNAs whether given at 7 or 28 days after ovariectomy. In contrast, whereas androgen replacement decreased alpha and LH beta mRNAs, D or T did not consistently suppress FSH beta mRNAs. We conclude that chronic estrogen administration to the castrated female rat uniformly suppresses all three gonadotropin subunit mRNA levels. In female rats, as in male rats, chronic androgen administration fails to negatively regulate FSH beta mRNAs.     

Divergent changes in the concentrations of gonadotropin beta-subunit messenger ribonucleic acid during the estrous cycle of sheep

Cyclic changes in the production of the pituitary gonadotrophic hormones, LH and FSH are essential events in the maintenance of the reproductive system of female mammals. While studies have examined changes in the secretion of LH and FSH during the estrous cycle and demonstrated the importance of these hormones in regulation of ovarian development and gametogenesis, considerably less is known concerning the regulation of the biosynthesis of these hormones. Although initial studies have examined changes in LH subunit mRNA concentrations during the rat and ovine estrous cycles, no information concerning the physiological regulation of FSH beta mRNA concentrations has been available. In the present study we have examined the relationship between pituitary concentrations of LH and FSH subunit mRNAs and the serum concentrations of these gonadotropins. The results demonstrate a very different pattern of change for FSH beta subunit mRNA than that observed for alpha and LH beta subunit mRNAs. In fact, FSH beta mRNA concentration decline substantially during the preovulatory period, reaching minimal values at a time when alpha and LH beta mRNA levels are near maximal. Furthermore, this decline in FSH beta mRNA amounts occurs when serum FSH concentrations are maximal. Thus, FSH beta mRNA concentrations follow a very different pattern than that of serum FSH. In contrast, LH beta mRNA and serum LH concentrations tend to increase at the same time. These findings provide evidence that concentrations of LH beta and FSH beta mRNAs are likely regulated by different mechanisms.     

Patterns of gonadotrophin secretion associated with ovulation

A detailed analysis was made of circulating luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin throughout the estrous cycle in rats. Vaginal cytology was recorded daily for 18 or 23 days in 2 groups of adult female rats, 300 and 400 per group. The presence of distended uteri or tubal ova was noted at the time of exsanguination under ether anesthesia. Serum concentrations of LH, FSH, and prolactin were determined by radioimmunoassay. In 404 rats with regular 5-day cycles, all 3 hormones reached maximum concentrations on the afternoon of functional proestrus. During the next 3 days FSH decreased progressively, and LH levels indicated a diurnal fluctuation with minimum concentrations during darkness. Serum prolactin may have b een elevated due to anesthesia and exsanguination and showed a rapid increase which occurred simultaneously with elevated LH and FSH on the afternoon of proestrus. Radioimmunoassay of all 3 hormones indicated that the increases in serum LH and prolactin did not necessarily occur simultaneously. Hypophysectomy and sequential heart puncture of proestrus rats during maximum hormone release showed disappearance rates (half-lives) for LH, FSH, and prolactin of 20, 110, and 13 minutes, respectively.     

Testosterone selectively increases serum follicle-stimulating hormonal (FSH) but not luteinizing hormone (LH) in gonadotropin-releasing hormone antagonist-treated male rats: evidence for differential regulation of LH and FSH secretion

Both testosterone (T) and gonadotropin-releasing hormone (GnRH)-antagonist (GnRH-A) when given alone lower serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in intact and castrated rats. However, when graded doses of testosterone enanthate (T.E.) were given to GnRH-A-treated intact male rats, a paradoxical dose-dependent increase in serum FSH occurred; whereas serum LH remained suppressed. This surprising finding led us to ask whether the paradoxical increase in serum FSH in GnRH-A-suppressed animals was a direct stimulatory effect of T on the hypothalamic-pituitary axis or the result of a T effect on a testicular regulator of FSH. To test these hypotheses, we treated adult male castrated rats with GnRH-A and graded doses of T.E. In both intact and castrated rats, serum LH remained undetectable in GnRH-A-treated rats with or without T.E. However, addition of T.E. to GnRH-A led to a dose-dependent increase in serum FSH in castrated animals as well, thus pointing against mediation by a selective testicular regulator of FSH. These data provide evidence that pituitary LH and FSH responses may be differentially regulated under certain conditions. When the action of GnRH is blocked (such as in GnRH-A-treated animals), T directly and selectively increases pituitary FSH secretion.     

Puberty and ovulatory release of gonadotropins in spontaneously hypertensive rats

The age at vaginal opening, estrous cyclicity, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) on the day of proestrus, and number of ova and ovarian weight as measured on the day of estrus in spontaneously hypertensive (SH) and genetically matched normotensive Wistar Kyoto (WKY) female rats were compared. In SH rats, there was a significant delay in the vaginal opening, but the regular 4-day estrous cycle followed afterwards. No significant changes were observed in the afternoon increase in serum LH, FSH and PRL on the day of proestrus in SH and WKY rats, although the basal levels of LH and PRL in the morning (11:00 h) were lower in SH rats than in WKY rats. The mean number of ova in SH rats was also less than in WKY rats, whereas the ovarian relative weight was similar in both species of rats. It can be said that SH rats undergo certain, but not critical, endocrine and/or neuroendocrine changes related to reproduction.     

Prolactin-releasing effect of tryptolines in the developing and adult male and female rats

The developmental prolactin-releasing effect of Tryptoline (T), Methoxytryptoline (MT) and Hydroxytryptoline (OHT) was examined comparatively in male and female rats. A single injection of T 15 mg/Kg increased serum prolactin in both sexes; the increase was significant from day 20 onwards. OHT evoked a sharp rise in 12 day-old rats and the releasing effect increased with age, both in males and females. No significant sex differences were observed in T or OHT treated rats. MT caused an increment in prolactin secretion in male rats and this action increased with age. The releasing effect of MT was not significant in females, even at 38 postnatal days. In adult animals, the tryptolines (15 mg/Kg) were able to increase serum prolactin in males and in females in diestrous; a dose of 5 mg/Kg of T was only effective in adult male rats. The prolactin-releasing effect was drastically reduced by orchidectomy and by ovariectomy. LH, FSH and TSH were not modified by any treatment. The present results show for the first time the ontogeny of the prolactin-releasing effect of tryptolines in male and female rats and that this effect depends on the presence of gonadal secretions in adults.     

Equine luteinizing hormone possesses follicle-stimulating hormone activity in hypophysectomized female rats

The ability of equine luteinizing hormone (eLH) to promote follicular growth and maturation in hypophysectomized rats has been assessed. A single injection of equine LH has been shown to promote the growth of a large number of antral and preovulatory follicles. In addition, equine LH markedly increased serum estrogen levels and uterine weight. Furthermore, equine LH, like equine chorionic gonadotropin (eCG; PMSG) was able to significantly enhance the incorporation of [3H]thymidine into ovarian DNA, an activity shown to be specific to hormones having follicle-stimulating hormone (FSH) activity. Equine LH treated with an FSH antibody immunoaffinity column to remove any possible contamination still exhibited the above activity, demonstrating that the FSH activity is intrinsic to the eLH molecule. Equine LH has also been shown to be capable of inducing LH receptors in granulosa cells of ovaries of hypophysectomized rats, an activity specific to FSH-like hormones. From the doses required of eLH and the degree of response observed, it is concluded, however, that eLH in the hypophysectomized rat is less active than eCG as an FSH.     

D-半乳糖诱导建立的小鼠多囊卵巢综合征模型

目的研究D-半乳糖诱导ICR中年雌性小鼠多囊卵巢综合征(PCOS)动物模型的卵巢形态学、性激素以及胰岛素水平变化,并探讨D-半乳糖引致小鼠PCOS的意义。方法以D-半乳糖腹腔注射20周龄ICR雌性小鼠8周,观察卵巢形态的变化,检测血糖值及动情周期排卵情况,并采用ELISA法测定血清胰岛素、雌二醇(E2)、促卵泡生长激素(FSH)、睾酮(T)水平。结果 D-半乳糖处理组小鼠的卵巢重量显著高于对照组(P<0.05),有80%(10/12)的单侧或双侧卵巢呈现多囊性扩张,卵巢闭锁增多及颗粒细胞层数减少,并表现为紊乱的动情周期,提示无排卵;与对照组比较,D-半乳糖组小鼠血清T、E2和空腹血糖水平明显升高(P<0.001),FSH水平下降(P<0.0001),空腹血胰岛素水平显著高于对照组(P<0.01),胰岛素敏感指数显著低于对照组(P<0.05)。结论使用D-半乳糖诱导小鼠PCOS模型,无论在影响血清性激素还是卵巢局部形态学改变方面都与临床表现相似,并存在胰岛素抵抗现象,符合PCOS的典型特征,可作为动物模型用于科学研究。     

Prepubertal treatment with estrogen or testosterone precipitates the loss of regular estrous cyclicity and normal gonadotropin secretion in adult female rats

To examine the effects of prepubertal steroid environment on subsequent estrous cyclicity and gonadotropin secretion, Silastic implants containing 25, 50 or 100% 17 beta-estradiol (E2;n=34), 50% diethylstilbestrol (DES; n=16) or 50% testosterone (T; n=17) were placed into female rats at 12 days of age and removed on the day of vaginal opening (18-24 days of age). At 80 days of age, the percentages of regularly cycling females in the E2-(three groups combined), DES- and T-implanted groups were 59%, 0% and 59%, respectively. By 110 days of age, the percentages were reduced to 24%, 0% and 0%, and at 140 days of age 6%, 0% and 0%, respectively. Many of these females displayed irregular estrous cycles followed by a persistent estrous (PE) state. By contrast, 89% of the control females (blank implants or no implant) maintained regular cycles up to 140 days of age. At 150 days of age, an i.p. injection of gonadotropin-releasing hormone (GnRH; 100 ng/100 g BW) markedly increased serum luteinizing hormone (LH), but not follicle-stimulating hormone (FSH), in intact PE females treated prepubertally with E2 implants. After the test with GnRH, PE rats were ovariectomized (OVX). Thirty days after OVX, similar GnRH administration significantly increased serum levels of both LH and FSH, but these responses were significantly (P less than 0.01) reduced when compared with those in OVX controls. Progesterone administration to estradiol benzoate-primed, acutely (3 days) OVX, or long-term (43 days) OVX-PE females did not increase LH or FSH release. These results indicate that exposure to exogenous estrogen or T prior to puberty precipitates the decline in estrous cyclicity associated with the loss of gonadotropin surge response, presumably due to an alteration in hypothalamic GnRH release.     

The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in female Syrian hamsters

Since melatonin injections administered near the end of the daily photoperiod influence both gonadal and thyroid hormones in the female hamster, the present study was designed to compare the effects of melatonin and hypothyroidism on the reproductive system and to determine whether thyroid status influenced the action of melatonin on the regulation of the hormones of reproduction. The effects of daily melatonin injections were determined in control hamsters, in hamsters rendered hypothyroid with thiourea, and in hypothyroid hamsters receiving thyroxin (T4) hormone replacement. As previously reported, melatonin injections disrupted estrous cyclicity, disrupted the normal pattern of gonadotropin secretion, and resulted in atrophy of the uterus and vagina. These changes coincided with depressed serum and pituitary prolactin (PRL), and depressed levels of estradiol. The effects of melatonin on uterus, vagina, ovary, and on gonadotropin levels were not prevented by T4 replacement, with the exception of a melatonin-induced increase in serum follicle-stimulating hormone (FSH). This suggested that the cessation of estrous cyclicity was not primarily a result of thyroid deficiency. Hypothyroidism, however, like melatonin, resulted in a reduced number of developing and mature follicles and corpora lutea in the ovaries, and in reduced uterine weight. It also produced follicular atresia, reduced the circulating levels of estradiol, and resulted in reduced incidence of estrus smears. T4 replacement, for 2 weeks, prevented the decline in mature follicles and corpora lutea, reduced the extent of follicular atresia, increased circulating levels of estradiol, and increased uterine weight. PRL and luteinizing hormone (LH) data also provided evidence for antagonistic effects of melatonin and T4 in female hamsters. These data raise the question whether melatonin-induced changes in circulating levels of T4 play a role in the seasonal cycles of reproductive competence in the female hamster.     

正常月经周期妇女卵泡液中激素水平的变化

本文测定了24例正常月经妇女在不同时相、不同大小卵泡的卵泡液中雌二醇(E_2)、孕酮(P_0)、雄烯二酮(A)、睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)和催乳素(PRL)的含量,并分析其与外周血中相应激素浓度的关系。测定结果显示:小卵泡的卵泡液中E_2、Po,FSH,LH水平低于大卵泡中水平,而A和T水平则相反。排卵前大卵泡中E_2(9815nmol/L),P_0(3316nmol/L),FSH(1.34IU/L)和LH(3.9lIU/L)达最高值。A(280nmol/L)和T(137nmol/L)却较小卵泡中水平低(相应为692nmol/L和176nmol/L)。PRL水平在大小卵泡中无显著性差异。卵泡液中甾体激素水平高于外周血7—20.000倍,FSH、LH水平为外周血的10—80％,PRL水平为60％—3倍。     

Functional and morphological changes in the hypothalamo-pituitary-gonadal axis of aged female rats.

Age-related functional and morphological alterations in the hypothalamo-pituitary-gonadal axis were investigated in old recurrently pseudopregnant (RPP) female rats, and these alterations were compared with those in young diestrous rats. LHRH in the median eminence (ME) and mediobasal hypothalamus (MBH) as well as plasma FSH, LH, and progesterone were measured by RIA. LHRH in the lateral ME (LME) and pituitary FSH and LH were evaluated by morphometry and densitometrical immunocytochemistry. Furthermore, by light microscopy, we classified and counted the number of ovarian follicles and corpora lutea. LHRH concentrations in the ME and MBH were similar in old and young rats, whereas in old rats, plasma FSH was markedly increased, LH was moderately increased, and plasma progesterone was unchanged. The number and the total area and immunoreactivity of LHRH-labeled axon cross sections in the LME were reduced in old rats. The number of nucleated FSH-labeled cells and total FSH area and immunoreactivity were almost twice in old compared with young animals. The measurements of LH-labeled cells were not different between the two groups. In old rats, the numbers of ovarian follicles and corpora lutea were reduced and that of atretic follicles increased. In conclusion, age-related morphological impairments of LHRH axons associated with an increased number of FSH gonadotropes and higher plasma FSH in our old RPP rats suggest hypothalamic and pituitary disturbances, which may largely contribute to the complex hormonal disarrangement responsible for the decline of reproductive functions in old female rats.     

Inhibin activity and secretion of gonadotropin during the period of follicular maturation

To evaluate the relative contributions of the ovarian inhibin and estradiol-17 beta (E) on the regulation of FSH secretion, inhibin and E in ovarian venous plasma (OVP) and FSH and LH in peripheral plasma were simultaneously measured using superovulating rats with special reference to follicular maturation. By the transplantation of a pituitary gland from adult male rats under the kidney capsule between 1100 and 1200 hr on diestrus-1 in cyclic rats, superovulation was successfully induced on the morning of the next estrus without any additional treatment with human chorionic gonadotropin (hCG). The number of maturing follicles capable of ovulating in response to hCG significantly increased at 12 hours after the grafting as compared with sham-operated controls and further increases occurred until the afternoon of proestrus. In the superovulating rat, first and second surges of FSH were completely blocked and an LH surge was also partially suppressed during the periovulatory period when surges of FSH and LH were normally observed in controls. Contents of FSH as well as LH in the animal's own pituitary gland were suppressed significantly after the grafting as compared with controls. A marked increase in inhibin activity in OVP of rats with a pituitary transplant occurred concomitantly with an increase in the number of follicles capable of ovulating whereas E levels in OVP did not so. Inhibin activity in OVP at each point was much higher in the pituitary grafted rats than in controls but this was not true for E levels. These results suggest that ovarian inhibin derived from the maturing follicles rather than E may be a primary factor for regulation of FSH secretion, and high levels of endogenous inhibin can suppress synthesis of LH as well as FSH in the pituitary gland of the female rat.     

Acute and chronic effects of the fornix section on cyclic gonadotropin secretion and ovulation in the rat.

The fornix was sectioned in the frontal plane by means of a razor blade knife, and acute and chronic effects of this section on gonadotropin secretion were estimated. The 5-day cyclic rat which received the section of fornix under either anesthesia at 12:00 on the day of diestrus II showed advancement of the proestrous and estrous vaginal smears and as well as ovulatory gonadotropin release by one day. It was revealed that the primary effect was the inducement of FSH release on the day of section. The 4-day cyclic rat bearing the fornix section chronically resumed vaginal cyclicity after elapsing the diestrous period for 18 to 25 days. The rat ovulated normally and mean number of ova inoviducts was not different from that in the intact rat. However, the sectioned rat hadan higher concentrations of pituitary and serum FSH on the day of diestrus II than thatin the intact rat, and had an higher concentration of serum LH on the day of estrus. These results indicate that the hippocampus exerts the inhibitory influence on LH and FSH release and if this is eliminated the facilitatory influence dominates the brain mechanism controlling gonadotropin release, resulting in the advancement of estrous cycle (the acute effect) or the increase of gonadotropin release (the chronic effect).     

Basal gonadotropin hormone release rates during the period of selective follicle-stimulating hormone release in the juvenile female rat

There are situations in which adult female rats release increased amounts of follicle-stimulating hormone (FSH) independent of increased luteinizing hormone (LH) release. This results from, at least in part, a selective increase in the basal FSH release rate. We investigated whether an increase in the basal FSH release rate is contributory to the rise in serum FSH levels which occurs independent of a rise in serum LH levels in the immature female rat. Rats had high serum FSH concentrations on days 7 and 15 after birth, low serum FSH levels on day 23, and low serum LH levels on all three days. In contrast, anterior pituitary gland (APG) FSH and LH concentrations and contents increased from day 7 to day 15 and the contents increased further from day 15 to day 23. Similarly, basal FSH and LH release rates per mg APG or per APG, as assessed by measurement of FSH and LH released into culture medium containing APG(s) from different aged rats, increased from day 7 to day 15 but did not increase further between days 15 and 23. The results indicate that unlike situations observed to date in adult female rats, a mechanism(s) other than an increase in the basal FSH release rate is involved in selective FSH release in the immature female rat.     

The role of estrogen in the feedback regulation of follicle-stimulating hormone secretion in the female rat

Letrozole (CGS 20267) is a non-steroidal aromatase inhibitor which, at its maximally effective dose of 1 mg/kg p.o., elicits endocrine effects equivalent to those seen after ovariectomy. Adult, female cyclic rats were administered letrozole (1 mg/kg p.o.) once daily for 14 days. A control group of animals was ovariectomized on day 1 of treatment and a third group of animals served as untreated controls. During the experiment, vaginal smears were taken daily and at the end of 14 days all animals were sacrificed, trunk blood was taken for serum estradiol, LH and FSH measurements and the uterus and ovaries were removed and weighed. The ovaries were then fixed and prepared for histological examination. Serum hormone measurements showed that after treatment with letrozole, serum estradiol levels were reduced by 76% of untreated controls and serum LH was elevated to 378% of control values. These compared favorably with those seen after ovariectomy, serum estradiol was reduced by 78% and serum LH was elevated to 485% of untreated controls. However, FSH was unchanged after letrozole treatment (125% of control), whereas after ovariectomy FSH rose to 398% of control. Uterine weight was suppressed in the letrozole-treated animals as well as the ovariectomized animals by 60 and 70%, respectively. The histology of the ovaries of animals treated with letrozole were consistent with the serum hormone findings. Except for the effects on serum FSH, these results confirm previous findings that treatment with letrozole elicits endocrine effects similar to those seen after ovariectomy. Furthermore, these results demonstrate that FSH secretion is not under the control of estradiol whereas LH secretion is under feedback control of ovarian estrogen.