Endocrine consequences of continuous antiestrogen therapy with tamoxifen in premenopausal women.
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Daily administration of estrogen antagonists to premenopausal women has been incorporated into the adjuvant treatment of breast cancer. We have studied the changes in reproductive hormones, pituitary responses to hypothalamic-releasing hormones, and endometrial histology during treatment with the antiestrogen tamoxifen in five healthy, premenopausal women. These studies were carried out during one menstrual cycle before and during two cycles of antiestrogen treatment. All subjects continued to have regular menses with biphasic basal body temperature records. During treatment, estradiol (E2) levels were increased but followed the usual pattern reflecting follicular maturation and corpus luteum formation. The mean E2 concentration at the midcycle peak and during the luteal phase was twice that observed during the non-treatment cycle. By contrast, the concentrations and secretory patterns of luteinizing hormone and follicle-stimulating hormone were not greatly changed, and the gonadotropin responses to gonadotropin-releasing hormone were not suppressed. Endometrial biopsies obtained during the follicular phase of control and tamoxifen treatment cycles showed no differences whereas biopsies obtained during the luteal phase of tamoxifen cycles uniformly showed a lack of changes attributed to progesterone action with no progression of histologic changes beyond those expected on day 7-8 of the luteal phase. These observations are consistent with maturation of multiple ovarian follicles, a surprising finding considering the normal gonadotropin concentrations. The retarded development of the endometrium in the presence of supranormal serum E2 and progesterone concentrations is a morphologic demonstration of the antiprogestational effect of antiestrogens. The lack of gonadotropin suppression in the presence of hyperestrogenemia suggests a major antiestrogen action on the hypothalmus and pituitary gland. (+info)
An improved computational method to assess pituitary responsiveness to secretagogue stimuli.
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OBJECTIVE: The quantitative assessment of gland responsiveness to exogenous stimuli is typically carried out using the peak value of the hormone concentrations in plasma, the area under its curve (AUC), or through deconvolution analysis. However, none of these methods is satisfactory, due to either sensitivity to measurement errors or various sources of bias. The objective was to introduce and validate an easy-to-compute responsiveness index, robust in the face of measurement errors and interindividual variability of kinetics parameters. DESIGN: The new method has been tested on responsiveness tests for the six pituitary hormones (using GH-releasing hormone, thyrotrophin-releasing hormone, gonadotrophin-releasing hormone and corticotrophin-releasing hormone as secretagogues), for a total of 174 tests. Hormone concentrations were assayed in six to eight samples between -30 min and 120 min from the stimulus. METHODS: An easy-to-compute direct formula has been worked out to assess the 'stimulated AUC', that is the part of the AUC of the response curve depending on the stimulus, as opposed to pre- and post-stimulus spontaneous secretion. The weights of the formula have been reported for the six pituitary hormones and some popular sampling protocols. RESULTS AND CONCLUSIONS: The new index is less sensitive to measurement error than the peak value. Moreover, it provides results that cannot be obtained from a simple scaling of either the peak value or the standard AUC. Future studies are needed to show whether the reduced sensitivity to measurement error and the proportionality to the amount of released hormone render the stimulated AUC indeed a valid alternative to the peak value for the diagnosis of the different pathophysiological states, such as, for instance, GH deficits. (+info)
Stimulatory effects of gonadotropin-releasing hormone and dopamine on growth hormone release and growth hormone mRNA expression in Epinephelus coioides.
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Gonadotropin-releasing hormone (GnRH) and dopamine (DA) can stimulate growth hormone (GH) release, but their effects on GH mRNA synthesis are controversial and deficient in fish. Orange-spotted grouper (Epinephelus coioides) is a hermaphroditic marine fish with sex reversal. Few data are available concerning the regulation of GH in grouper. In the present study, the effects of GnRH and DA on GH release and GH mRNA expression were determined using pituitary fragments of orange-spotted grouper under static culture conditions. After incubation from 1 h to 24 h, salmon GnRH (sGnRH, 100 nmol/L) stimulated the release of GH and increased the level of GH mRNA time-dependently. The minimum duration of sGnRH effect was 1 h. Both of sGnRH and mammalian GnRH (mGnRH) augmented the release of GH and the level of GH mRNA in a dose-dependent manner. The potency of sGnRH on both GH release and GH mRNA level was more pronounced than that of mGnRH. The effects of 1 micromol/L APO (Apomorphine), an agonist of D(1)/ D(2) dopamine receptors, significantly stimulated GH release and GH mRNA synthesis after incubation for 12 h. APO stimulated GH release and GH mRNA abundance in a dose-dependent manner. These results demonstrate that both GnRH and DA directly stimulate GH release and GH mRNA expression at the pituitary level, the actions of GnRH are more potent than that of DA in orange-spotted grouper. (+info)
Regulative actions of the Chinese drugs for tonifying the kidney on gene expression of the hypothalamic GnRH, pituitary FSH, LH and osteoblastic BGP.
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It is found that the drugs for nourishing yin to reduce pathogenic fire can significantly down-regulate, and the drugs for tonifying the kidney to replenish essence can up-regulate mRNA expression of the hypothalamic GnRH, pituitary FSH, LH and osteoblastic BGP, indicating that the Chinese drugs for tonifying the kidney can regulate gene expression of the hypothalamic GnRH, pituitary FSH, LH, and osteoblastic BGP, which is possibly one of the main mechanisms of the Chinese drug for tonifying the kidney, regulating ephebic development process andimproving skeletal development in sexual precocity children. (+info)
Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action.
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It has been shown previously that female mice homozygous for an alpha-fetoprotein (AFP) null allele are sterile as a result of anovulation, probably due to a defect in the hypothalamic-pituitary axis. Here we show that these female mice exhibit specific anomalies in the expression of numerous genes in the pituitary, including genes involved in the gonadotropin-releasing hormone pathway, which are underexpressed. In the hypothalamus, the gonadotropin-releasing hormone gene, Gnrh1, was also found to be down-regulated. However, pituitary gene expression could be normalized and fertility could be rescued by blocking prenatal estrogen synthesis using an aromatase inhibitor. These results show that AFP protects the developing female brain from the adverse effects of prenatal estrogen exposure and clarify a long-running debate on the role of this fetal protein in brain sexual differentiation. (+info)
Major phases of the physiology of food intake regulation remain hypothetical. There is a central regulatory mechanism for hunger and satiety, but the signals and messages that activate the brain centers remain conjectural. The alimentary tract regulation, the regulation by osmoreceptors, the thermostatic, the glucostatic, the lipostatic, the amino acid, and the hormonal food intake regulation theories leave many questions unanswered. Low molecular weight peptides appear to have an important effect on brain functions. Hypothalamic peptides such as thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin have been assigned new roles in various brain functions. The hypothalamus and probably other parts of the brain produce also anorexigenic peptides. Anorexia is a common manifestation of cancer. It is proposed that peptides, oligonucleotides, and other small metabolites produced by the cancer and by the tumor-bearing host are responsible for the genesis of the anorexia. They produce the anorexia through a peripheral effect on neuroendocrine cells and neuroreceptors and through a direct effect on hypothalamic and other central nervous system sensor and responder cells. (+info)
Secretory patterns of LH and FSH during development and hypothalamic and hypophysial characteristics following development of steroid-induced ovarian follicular cysts in dairy cattle.
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Two experiments were conducted to (1) investigate developmental endocrinology of ovarian follicular cysts (cysts) in cattle and (2) evaluate effects of cysts on hypothalamic and hypophysial characteristics. Cysts were induced with oestradiol-17 beta (15 mg) and progesterone (37.5 mg) dissolved in alcohol and injected s.c. twice daily for 7 days. Cysts were defined as the presence of follicular structures (which may or may not have been the same structure) of 2.0 cm in diameter or greater that were present for 10 days without ovulation and corpus luteum development. In Exp. 1,22 non-lactating, non-pregnant Holstein cows were allocated to 3 groups. Beginning on Day 5 (oestrus = Day 0) of the oestrous cycle, 7 cows (Controls) were treated with twice daily s.c. injections of ethanol (2 ml/injection) for 7 days. Luteolysis was then induced with PGF-2 alpha and blood samples were collected daily every 15 min for 6 h from the morning after the PGF-2 alpha injection (Day 13) until oestrus. Steroids to induce cysts were injected as previously described into the remaining cows (N = 15). Three blood samples were collected at 15-min intervals every 12 h throughout the experimental period. Additional blood samples were collected every 15 min for 6 h on a twice weekly basis. After steroid injections, follicular and luteal structures on ovaries were not detected via rectal palpation for a period of 36 +/- 4 days (static phase). Then follicles developed which ovulated within 3-7 days (non-cystic; N = 7) or increased in size with follicular structures present for 10 days (cystic; N = 8). Mean (+/- s.e.m.) concentrations of LH, FSH, oestradiol-17 beta and progesterone in serum remained low and were not different during the static phase between cows that subsequently developed cysts or ovulated. During the follicular phase, mean serum concentration of LH (ng/ml) was higher (P less than 0.1) in cows with cysts (2.9 +/- 0.2) than in cows without cysts (1.1 +/- 0.1) or control cows (1.4 +/- 0.2). In addition, LH pulse frequency (pulses/6 h) and amplitude (ng/ml) were higher (P less than 0.1) in cows with cysts (3.6 +/- 0.3 and 2.2 +/- 0.3, respectively) than in non-cystic (2.3 +/- 0.2 and 1.0 +/- 0.2, respectively) and control (1.8 +/- 0.1 and 1.1 +/- 0.2, respectively) groups during the follicular phase. There were no differences in the FSH, oestradiol-17 beta or progesterone characteristics in cows of any of the 3 groups during the follicular phase.(ABSTRACT TRUNCATED AT 400 WORDS) (+info)
Developmental changes in pituitary-gonadal function in free-ranging lions (Panthera leo leo) of the Serengeti Plains and Ngorongoro Crater.
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Pituitary-gonadal function was examined in male lions free-ranging in the Serengeti Plains or geographically isolated in the Ngorongoro Crater of Tanzania. Lions were classified by age as adult (6.1-9.8 years), young adult (3.3-4.5 years) or prepubertal (1.4-1.6 years, Serengeti Plains only). Each animal was anaesthetized and then bled at 5-min intervals for 100 min before and 140 min after i.v. administration of saline or GnRH (1 micrograms/kg body weight). Basal serum LH and FSH concentrations were similar (P greater than 0.05) among age classes and between locations. In Serengeti Plains lions, net LH peak concentrations after GnRH were approximately 35% greater (P less than 0.05) in prepubertal than in either adult or young adult animals. GnRH-stimulated LH release was similar (P greater than 0.05) between adult and young adult lions, and these responses were similar (P greater than 0.05) to those measured in Ngorongoro Crater lions. Basal and GnRH-stimulated testosterone secretion was higher (P less than 0.05) in adult than in young adult lions and lowest (P less than 0.05) in prepubertal lions. Age-class differences in testosterone production were related directly to the concentrations of LH receptors in the testis (P less than 0.05). Basal and GnRH-stimulated testosterone secretion and gonadotrophin receptor concentrations within age classes were similar (P greater than 0.05) between lions of the Serengeti Plains and Ngorongoro Crater. Lower motility and higher percentages of structurally abnormal spermatozoa were observed in electroejaculates of young adult compared to adult Serengeti Plains males (P less than 0.05) and were associated with decreased steroidogenic activity. In contrast, there were no age-related differences in ejaculate characteristics of Ngorongoro Crater lions. Seminal quality in the Crater population was poor in adult and young adult animals and was unrelated to alterations in pituitary or testicular function. In summary, only seminal quality in adult male lions was affected by location, whereas age significantly affected both basal and GnRH-stimulated testosterone secretion and seminal quality (Serengeti Plains only) in sexually mature males. The striking seminal/endocrine differences among pride (breeding) males of different ages raises questions about the impact of age on individual reproductive performance in this species. (+info)