Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of hemicastrated adult female rats with adrenoblockers, chlorpromazine and alpha-methyl-DOPA decreased the ovarian compensatory hypertrophy (OCH) and prevented the stilbestrol suppression of the OCH. Disulfiram (dophamine-beta-hydroxylase inhibitor) potentiated the stilbestrol suppression of the OCH. Small doses of L-DOPA stimulated the OCH, and high doses of L-DOPA and dilantin failed to act on the ACH, but potentiated the estrogeninduced OCH inhibition. It is suggested that the FSH secretion was mediated by the release of norepinephrine in the central adrenergic neurons and that the estrogen action inhibiting the FSH secretion was mediated through the stimulation of dophamine release.
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PMID:[Pharmacologic study of adrenergic mechanisms of compensatory hypertrophy of the ovary]. 122 99

Four consecutive menstrual cycles were studied in six healthy parous women. A solvent mixture comprising propylene glycol:ethanol:water (3:3:4) was sprayed intranasally daily using a glass atomizer between days 5 and 24 of the first (control) menstrual cycle. NET was dissolved in the solvent and similarly administered at a daily dose of 100 mcg during the second and third menstrual cycles. Nasal sprays were not administered during the fourth post-treatment cycle. Blood samples were taken during four consecutive cycles between days 8 and 15 and again between days 20 and 24 of the cycle to estimate levels of estradiol (E2), FSH, LH and progesterone (P). These studies revealed that nasal sprays of NET were well accepted and that no adverse clinical effects or menstrual disturbances occurred. NET inhibited ovulation in one cycle. The E2-induced mid-cycle rise in FSH and LH was either suppressed or inhibited in nine out of the 12 treated cycles. P levels in three treated cycles were indicative of luteal inadequacy. These endocrine effects of NET persisted into the post-treatment cycle in two cases.
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PMID:Reproductive endocrine effects of intranasal administration of norethisterone (NET) to women. 393 71

The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25-26 days of age, and an Alzet osmotic minipump containing ACTH (1-24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 micrograms of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 +/- 94 vs 443 +/- 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats. 632 94

10 Egyptian women who were using the injectable contraceptive norethisterone enanthate (NET-EN) for at least 6 months were monitored weekly for a period of 12 weeks by measuring 3 pituitary hormones (FSH, LH, prolactin) and 2 ovarian hormones (estradiol 17-B and progesterone). It was concluded that NET-EN is a strong ovulation inhibitor, at least after its use for 6 months. Prolactin levels were depressed and this is in contrast to the findings in rats.
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PMID:Blood hormone levels in egyptian women on norethisterone oenanthate. 641 60

In a double-blind randomized trial, 25 women (8-9 weeks pregnant) received 20 mg norethisterone acetate (NET-AC) and 0.04 mg ethinylestradiol (EE2), 25 women receiving placebo. The patients were followed by ultrasound and the products at curettage studied macroscopically and microscopically. In an open trial, ten patients (5-9 weeks pregnant) received NET-AC + EE2, 11 serving as controls. The concentrations of plasma progesterone, estradiol-17 beta, 17 alpha-hydroxyprogesterone, norethisterone, and FSH were followed. The frequency of intrauterine hemorrhage in early pregnancy was not affected by NET-AC + EE2. Ultrasound was not reliable when studying the occurrence of decidual hemorrhages during early pregnancy. The pharmacokinetics and bioavailability of NET remain unchanged during early pregnancy. The treatment with NET-AC + EE2 had no effect on the heights and the time courses of the mean plasma values of progesterone, estradiol-17 beta, 17 alpha-hydroxyprogesterone, and FSH. No differences were found between treated and nontreated patients in the pathology of the placenta or decidua as determined by both macroscopic and microscopic examinations. The hypothesis of Papp and Gardo, that decidual hemorrhages may be induced in early pregnancy as a consequence of a "withdrawal effect" of hormonal pregnancy tests, is not supported by the results of this investigation.
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PMID:Norethisterone acetate and ethinylestradiol in early human pregnancy. 642 76

Twelve males with azoospermia secondary to exposure to the nematocide 1,2-dibromo-3-chloropropane were challenged to iv LRH (100 micrograms), TRH (200 micrograms), and metoclopramide (MET; 10 mg) administered 30 min apart. When compared to 24 male controls, both basal FSH and LH levels as well as peak gonadotropin responses to LRH were increased in the azoospermic group. The patients also had increased total estradiol (E2) and testosterone (T) as well as testosterone-binding globulins levels. Free T levels, however, were not significantly different from the controls. Basal PRL levels were similar in the two groups. However, the peak PRL responses to both TRH and MET were significantly increased in the azoospermia subjects (P < 0.001). In both groups, the PRL response to MET was greater than to TRH. In the individual control and azoospermic subjects, there was no correlation between the PRL response and E2, T, or the E2 to T ratio. However, a positive correlation did exist between testosterone-binding globulin levels and the PRL response to TRH and MET. Although the precise mechanism underlying the PRL hyperresponsiveness is unknown, it may be an estrogen-induced phenomenon.
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PMID:The exaggerated prolactin response to thyrotropin-releasing hormone and metoclopramide in 1,2-dibromo-3-chloropropane-induced azoospermia. 677 92

A clinical trial was conducted with 2 types of progestogen-only contraceptives in 20 fertile Cuban women. 1/2 the group was administered NEN (norethisterone enanthate) injectable; the other 1/2 was given NET (norethisterone acetate) minipill. Daily blood samples were taken and complicated laboratory procedures followed to measure pharmacological effects and gonadotropin secretion. Although preovulatory LH (luteinizing hormone) and FSH peaks were abolished, basal levels of these 2 hormones remained constant. 8 of the 10 women on NEN had some type of menstrual disorder; 5 of those on NET experienced menstrual disorders. Despite the menstrual irregularities, both drugs were highly acceptable and the continuation rate was high. No pregnancy was reported in either group. Blood pressure, renal, hepatic, and thyroid function remained unchanged. Cholesterol levels were unchanged. Both drugs significantly reduced triglycerides. The NET group registered significant changes in their carbohydrate metabolism.
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PMID:Phase I clinical trial of two contraceptive preparations. Norethisterone enanthate (NEN) and norethisterone acetate (NET). 678 25

6 normally menstruating women were each inserted with a single silastic implant-D releasing (NETA) norethindrone acetate. The levels of endogenous hormones, FSH, LH, E2, and progesterone, were estimated by (RIA) radioimmunoassay procedures in the control and treatment cycles. In addition, the levels of drug in the serum as (NET) norethindrone which is a major metabolite of NETA were also estimated by RIA procedures in the treatment cycles. In all, 12 treatment cycles were studied. In the initial treatment cycles (1st/2nd or 3rd), the serum NET levels were either 1 ng/ml or above. The LH and FSH showed either normal or suppressed midcycle peaks, but the progesterone levels were completely suppressed. In the 6th treatment cycle, the serum NET levels were either 0.5 ng/ml or below. The FSH and LH midcycle peaks were lower but distinct while the luteal progesterone levels were of normal ovulatory type. These studies lead us to the conclusion that a serum level of NET of the order of 1 ng/ml is required to bring about suppression of luteal progesterone, either as a result of direct action on the ovary or through suppression of pituitary gonadotropins. When the serum level falls to 0.5 ng/ml or below, the suppressive effect is removed and ovulatory pattern of progesterone returns.
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PMID:Correlation between the serum norethindrone (NET) levels attained after insertion of a silastic implant releasing norethindrone acetate and the endogenous hormones particularly progesterone. 678 28

Galanin (GAL) has recently emerged as an important neuroendocrine regulator which participates in the control of several pituitary and hypothalamic hormones. Our earlier observation that GAL stimulates LHRH release from nerve terminals of the median eminence as well as basal LH and LHRH-induced LH secretion from pituitary cells in vitro prompted us to evaluate whether endogenous GAL plays a role in regulation of the physiologically occurring preovulatory surges of gonadotropins and PRL. Proestrous female rats were passively immunized against GAL using a high affinity sheep antirat GAL serum (FMS-FJL 17-5). Animals were implanted during diestrus with indwelling atrial cannulae. On the expected day of proestrus, rats received 1 ml of either normal sheep serum or GAL antiserum (GAL-AS), iv, 1 h before blood sampling started. Blood samples (0.5 ml) were collected at hourly intervals from 1400-2300 h, and plasma levels of LH, FSH, and PRL measured by RIA. At several time intervals after GAL-AS administration, the maximum binding ability of the rat plasma was evaluated using standard saturation assays. High neutralizing levels of immunoglobulins were present throughout the experimental period. GAL passive immunization blunted the LH preovulatory surge by 30%. Although maximum LH levels were unaffected by the treatment, the area under the secretory curve and LH levels at 1700, 1900, and 2000 h were significantly reduced. Conversely, FSH secretion was not significantly altered for either maximum FSH levels or area under the curve. However, FSH levels were significantly diminished in GAL-AS-treated rats at 1700 h. GAL passive immunization selectively reduced the plateau phase of the preovulatory surge of PRL. No significant differences were observed in the initiation of the surge or maximum PRL levels, whereas PRL levels were significantly reduced from 1700 to 2200 h. In addition, the area under the PRL curve was diminished in GAL-AS-treated animals by 40%. In conclusion, our results clearly demonstrate that endogenous GAL is involved in control of the preovulatory surges of LH and PRL without altering the FSH surge. In addition, they provide, for the first time, evidence of an important role for endogenous GAL in the regulation of physiological events leading to ovulation.
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PMID:Endogenous galanin modulates the gonadotropin and prolactin proestrous surges in the rat. 767

The developing ovarian follicle is one of the most rapidly proliferating normal tissues in vivo. Mesenchymal-epithelial cell interactions between theca cells and granulosa cells are essential for this follicular expansion. Ovarian hormones (i.e. estrogen and LH) may promote follicular development by regulating the local production of mesenchymal inducer proteins that mediate theca cell-granulosa cell interactions. Recently, theca cells were shown to produce keratinocyte growth factor (KGF) that can act in a paracrine manner to stimulate granulosa cell growth. In this study, the developmental and hormonal regulation of KGF was examined during follicular development in the bovine ovary. Expression of KGF in theca cells and the KGF receptor (KGFR, or splice variant of the fibroblast growth factor family receptor family, FGFR-2) in granulosa cells was examined using RT-PCR. Both KGF and KGFR were detected throughout follicular development in small (<5 mm), medium (5-10 mm), and large (>10 mm) follicles. Quantitative RT-PCR assays were used to determine steady-state levels of KGF and KGFR messenger RNAs. Developmental regulation of KGF and KGFR was analyzed in freshly isolated theca cells and granulosa cells from small, medium, and large follicles. Observations demonstrated that expression of KGF (in theca cells) and KGFR (in granulosa cells) was highest in large follicles. These results suggest that KGF actions are important for the rapid proliferation of granulosa cells in large follicles. Estrogen and LH are the primary endocrine hormones that regulate theca cell function in vivo. Therefore, hormonal regulation of KGF was analyzed by treating serum-free theca cell cultures with estrogen and human CG (hCG, an LH agonist). Results showed that both estrogen and hCG stimulated KGF gene expression in theca cells. These results suggest that estrogen and LH may promote follicular growth (i.e. granulosa cell proliferation), in part, by stimulating the local production of KGF. Effects of KGF on granulosa cell differentiated functions were examined. Treatment with KGF reduced basal levels and FSH-stimulated levels of aromatase activity in bovine and rat granulosa cells. In addition, KGF inhibited the ability of hCG to stimulate progesterone production by granulosa cells. The inhibition of granulosa cell steroid production by KGF was likely the indirect effect of promoting cellular proliferation. Therefore, KGF directly stimulates granulosa cell proliferation and indirectly inhibits granulosa cell differentiated functions. Combined results suggest that theca cell production of KGF may be important for ovarian folliculogenesis. This is the first report of the regulation of KGF expression in the ovary. The developmental and hormonal regulation of KGF and KGFR during folliculogenesis provides evidence that KGF may be important for hormone-induced granulosa cell proliferation. As a result, KGF may be essential for establishing the microenvironment required for oocyte maturation in the ovary.
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PMID:Developmental and hormonal regulation of keratinocyte growth factor expression and action in the ovarian follicle. 942 19


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