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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine therapy is a major treatment modality for the systemic management of breast cancer. In comparison with alternatives such as chemotherapy, hormone manipulations have the advantage of lower toxicity but suffer from the disadvantages of producing responses in only 30-40% of patients with metastatic disease and seldom being curative. Nevertheless in recent years there have been significant advances in the endocrine treatment of breast cancer which have stemmed from a better understanding of the sources from which breast tumours may be supplied with hormones, the mechanism by which hormones regulate tumour proliferation and the more accurate identification of hormone sensitive tumours. As a result agents such as antioestrogens, aromatase inhibitors. LHRH agonists have largely superseded surgical and radiological ablation of endocrine organs. The major reduction in morbidity associated with these medical regimes means that they are much more acceptable to patients and may be used as adjuvants to local treatment of the breast in patients with "earlier" stages of the disease. At the same time patients can now be offered rational treatment selected on the basis of tumour biology rather than on more empirical criteria. The aims of this review are to provide details of the research which has led to this progress in endocrine treatment of breast cancer and to put into perspective the prospects for further advances.
J Steroid Biochem Mol Biol 1990 Nov 30
PMID:Endocrine treatment for breast cancers: biological rationale and current progress. 227 30

Three hundred and sixty-three patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6,des-Gly-NH2(10)]LHRH ethylamide (or orchiectomy) for an average of 771 days (24-2607 days). Only 31 of the 308 evaluable patients (10.1%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in five recent studies using monotherapy. The median survival achieved using monotherapy is approximately 24 months while, in the present study, it is increased to 41.2 months, thus giving an additional 17 months of survival with the combination therapy. It should be mentioned that at the time of relapse, combination therapy is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide and hydrocortisone. While our studies showing the advantages of combination therapy with pure antiandrogen in advanced prostate cancer have been confirmed by independent large-scale randomized studies, our preliminary data clearly suggest the interest of downstaging early stage prostate cancer by temporary combination therapy prior to radical prostatectomy.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Combination therapy with flutamide and medical (LHRH agonist) or surgical castration in advanced prostate cancer: 7-year clinical experience. 228 8

Histopathological changes induced by immune responses generated against luteinizing hormone releasing hormone (LHRH) were studied in adult male Wistar rats. Active immunization with a semisynthetic anti-LHRH vaccine, LHRH D-Lys6, (10, 40, and 80 micrograms/animal) conjugated with diphtheria toxoid, produced bioeffective antibodies as indicated by significant reduction in circulating testosterone levels. At the 14th week after immunization the animals were sacrificed and reproductive organs were evaluated. These organs were studied for histopathological changes and compared with those of nonimmunized control rats. Marked hypoplastic changes were observed in the genital organs. Testicular changes such as arrest of spermatogenesis at the spermatocyte level and atrophic changes in the interstitial Leydig cells were noticed in treated animals. Similarly attenuation of secretory epithelial cells with substantial increase in the stromal tissues was observed in the prostate and seminal vesicles. The current observation suggests the possible usefulness of this anti-LHRH vaccine under clinical conditions where reduction in androgenic response is desired as in the case of hormone-dependent prostatic carcinoma.
Exp Mol Pathol 1990 Feb
PMID:Histopathological changes in reproductive organs of male Wistar rats following active immunization against LHRH. 240 46

A continuous flow superfusion system which was previously developed in our laboratory was utilized to study the modulation of LH and FSH release by cyclic nucleotides and LHRH from anterior pituitary glands (APG) obtained from rats or hamsters. There was a transient increase in LH and FSH secretion from superfused rat APG in response to superfusion with 1 X 10(-3) M 1-methyl-3-isobutyl-xanthine (MIX), while 1 X 10(-4) MIX M had no effect. Furthermore, a dose of 5 X 10(-5) M MIX did not potentiate the gonadotrophin-releasing effect of 1 X 10(-10) M LHRH. Neither 1 X 10(-3) M 8-Br-cAMP nor 1 X 10(-3) M 8-Br-cGMP mimicked the gonadotrophin-releasing effects of 1 X 10(-9) M LHRH. In the experiments utilizing hamster APG, FSH release gradually increased during superfusion with 1 X 10(-3) M MIX or 1 X 10(-4) M MIX, while LH release was transient but significantly increased in response to superfusion with both doses of MIX. A dose of 5 X 10(-5) M MIX potentiated the effect of a low dose of LHRH (1 X 10(-10) M) upon both LH and FSH secretion. 1 X 10(-3) M 8-Br-cAMP mimicked the effect of LHRH upon LH and FSH released from superfused hamster APG, while 1 X 10(-3) M 8-Br-cGMP was inhibitory. These results suggest that cyclic nucleotides are involved in the mediation of the LHRH-induced release of gonadotropins from the anterior pituitary gland of the hamster, but do not mediate the LHRH-induced release of gonadotropins from the rat anterior pituitary gland.
Mol Cell Endocrinol 1988 Feb
PMID:Differences in the cyclic nucleotide mediation of luteinizing hormone-releasing hormone action on the rat and hamster anterior pituitary gland. 245 26

The effect of incubation with LHRH and its agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide has been measured on the concentrations of mRNAs for the common alpha-subunit of glycoprotein hormones and beta-LH in rat anterior pituitary cells in primary culture. After incubation, total RNA was analyzed by Northern blot or dot blot hybridization with alpha- and LH beta 32P-labeled cRNA probes and mRNA levels were quantified by autoradiography. Short-term treatment (4-6 h) of pituitary cells with 100 nM LHRH led to a marked stimulation of LH release but no effect was observed on alpha-subunit or LH beta mRNA levels. Longer (24-72 h) incubation periods with LHRH led to complete desensitization of the LH response to the neurohormone and induced 2- to 3-fold increases in alpha-mRNA cell content while LH beta mRNA levels remained unchanged. Maximal induction of alpha mRNA accumulation was observed with an LHRH concentration as low as 0.1 nM. Incubation with the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide for 24-72 h also increased alpha mRNA but did not modify LH-beta mRNA levels. It is concluded that long-term exposure of anterior pituitary cells to LHRH or to an LHRH agonist positively regulates alpha-subunit gene expression in the absence of change in LH beta mRNA levels. This observation can provide an explanation for the high plasma levels of free alpha-subunits found in patients treated chronically with LHRH agonists.
Mol Endocrinol 1988 Jun
PMID:Effect of luteinizing hormone releasing hormone (LHRH) and [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide on alpha-subunit and LH beta messenger ribonucleic acid levels in rat anterior pituitary cells in culture. 245 26

LHRH and sex steroids play a major and direct regulatory role in the secretion of LH by the anterior pituitary gland. The aim of the present study was to investigate the interactions between sex steroids, more especially the potentiating effect of progesterone (P) in the presence or absence of a low dose of 17 beta-estradiol (E2) and/or dihydrotestosterone (D) on mRNA levels encoding the alpha- and beta-subunits of LH in both female and male rats. We also studied the effect of 2-week treatment with the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide on the same parameters. After treatment with the LHRH agonist (5 micrograms daily), the accumulation of mRNA encoding the alpha-subunit was stimulated by approximately 3-fold while the LH beta mRNA concentration remained unchanged. Ovariectomy performed 14 days earlier, increased pituitary alpha and LH beta mRNA levels by 3.7- and 8.8-fold, respectively, while orchiectomy performed 14 days earlier increased alpha and LH beta mRNA levels by 6- and 6.5-fold, respectively. The present data demonstrate that although P alone exerts no effect on alpha and LH beta mRNA levels in castrated animals, treatment with P markedly potentiates the inhibitory effect of E2 on both mRNA levels in female as well as male rats. In addition, P potentiates the inhibitory effect of D on LH beta mRNA levels in castrated female rats. Furthermore, the present study illustrates the importance of the cumulative inhibitory effects of relatively low doses of E2 and D on mRNAs encoding both LH subunits. Moreover, the present observation of a differential modulation of alpha-subunit and LH beta mRNA levels after chronic treatment with an LHRH agonist offers an explanation for the high plasma levels of free alpha-subunit found in patients treated with LHRH agonists.
Mol Endocrinol 1988 Sep
PMID:Modulation by sex steroids and [D-Trp6, Des-Gly-NH2(10)]luteinizing hormone (LH)-releasing hormone ethylamide of alpha-subunit and LH beta messenger ribonucleic acid levels in the rat anterior pituitary gland. 245 4

We have isolated and cloned the full length cDNA for mouse GH-releasing hormone (mGRH) from mouse hypothalamus using a recently described strategy involving the polymerase chain reaction technique (PCR). Degenerate oligonucleotide primers were selected based on short (six amino acids) conserved regions in the human and rat GRH peptides that would recognize DNA sequences encoding similar amino acids regardless of codon usage. Primer-extended cDNA was amplified by PCR on cDNA templates prepared by reverse transcribing total mouse hypothalamic RNA. After cloning and sequencing the initial product, the 3' and 5' ends of mGRH were generated using a separate PCR strategy (RACE protocol). The mGRH cDNA encodes a 103-amino acid reading frame, structurally similar to the human and rat GRH genes, containing a signal sequence, a 42-residue GRH peptide, and a 31-residue C-terminal region. Although the structures of mouse and rat GRH are highly conserved in the signal peptide and C-terminal region, there is considerable diversity in the GRH region, which exhibits nearly comparable homology with the rat (68%) and human (62%) structures. Differences between mouse and rat GRH were also found in the amino acid cleavage sites at the 5' and 3' ends of the mature peptide and at the polyadenylation signal.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Oct
PMID:Cloning and characterization of mouse growth hormone-releasing hormone (GRH) complementary DNA: increased GRH messenger RNA levels in the growth hormone-deficient lit/lit mouse. 248 13

In order to reveal the action of gonadotropin-releasing hormone (GnRH) on the synthesis of gonadotropins in the pituitary gland of castrated rats, passive immunization to GnRH designed to block the activity of GnRH was performed. The levels of prolactin mRNA in castrated and rabbit anti-GnRH serum (RAGnRH)-treated rats decreased, whereas TSH beta mRNA showed no statistically significant change. In contrast, mRNAs encoding common alpha, LH beta and FSH beta were increased 2.7-, 1.7- and 1.5-fold, respectively, by castration. These elevated mRNA levels of gonadotropin subunits in castrated rats well explain the increased hormone levels in serum and in the pituitary. Two days later, a single administration of RAGnRH to the castrated rats significantly suppressed the mRNA levels to 2.0-fold for alpha, 1.2-fold for LH beta and 1.1-fold for FSH beta relative to the respective control values. These results showed that the two gonadotropin beta genes respond more rapidly to GnRH action that the common alpha gene.
Mol Cell Endocrinol 1989 Mar
PMID:Simultaneous effect of gonadotropin-releasing hormone (GnRH) on the expression of two gonadotropin beta genes by passive immunization to GnRH. 250 Nov 22

Prostaglandin E2 (PGE2) is known to stimulate the release of luteinizing hormone releasing hormone (LHRH) from explants of the median eminence area (MEA). We have previously shown that a short preincubation of the MEA with copper markedly amplifies PGE2 stimulation of LHRH release and that the Ca2+-cAMP pathway is involved in this release process. In this study, we defined the kinetics of the onset of PGE2 action and examined the Ca2+ requirement for the onset and manifestation of PGE2 action. MEA explants from immature female rats were incubated with copper (150 microM copper-histidine complex); thereafter, explants were exposed to 10 microM PGE2 for periods of 2-7 min with or without Ca2+ (Ca2+-free buffer containing 1 mM EGTA). A 2 min PGE2 exposure was as effective as a 7 min PGE2 exposure in stimulating LHRH release; the latter was manifested during the period between 2-7 min. When MEA were exposed to PGE2 for 5 min, maximal rate of release was attained within this 5 min period. When MEA were exposed to PGE2 for 2 min and then to forskolin (100 microM) for 5 min, there was no further increase in the rate of LHRH release (although exposure to forskolin alone maximally stimulated LHRH release). In the presence of EGTA (no Ca2+), PGE2 stimulation of LHRH release was abolished and this effect of EGTA was totally reversed by the addition of Ca2+ 2 min after PGE2 exposure and partially reversed (40%) by the addition of Ca2+ 5 min after PGE2 exposure in the presence of EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1989 Aug
PMID:A rapid, Ca2+-independent, onset of prostaglandin E2 stimulation of the release of luteinizing hormone releasing hormone from copper-treated median eminence explants. 250 87

The effects of human chorionic gonadotropin (hCG) and prostaglandin F2 alpha (PGF2 alpha) on the adenylate cyclase-cAMP and inositol phospholipid-phospholipase C-inositol trisphosphate and diacylglycerol transmembrane signalling systems were evaluated in cultured human granulosa-luteal cells. Granulosa-luteal cells obtained from patients undergoing in vitro fertilization were cultured for 72 h prior to addition of hormones. During the last 24 h of culture granulosa-luteal cells were incubated with [3H]inositol. Neither hCG nor gonadotropin-releasing hormone (GnRH) stimulated the inositol phospholipid-phospholipase C signalling system. PGF2 alpha stimulated increases in inositol mono-, bis-, and trisphosphate accumulation in 30 min incubations. NaF (20 mM) mimicked the stimulatory effect of PGF2 alpha on inositol phosphate accumulation suggesting the involvement of a guanine nucleotide regulatory protein in the activation of phospholipase C. In contrast, hCG but not PGF2 alpha or NaF stimulated cAMP accumulation in 30 min incubations. Simultaneous treatment with hCG and PGF2 alpha did not alter the stimulatory effect of PGF2 alpha on inositol phosphate accumulation but reduced (37%) the stimulatory effect of hCG on cAMP accumulation. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited the stimulatory effects of hCG (76%) and PGF2 alpha (62%) on cAMP and inositol phosphate accumulation, respectively. Thus, cultures of human granulosa-luteal cells possess multiple transmembrane signalling systems which may be modulated by the activation of protein kinase C.
Mol Cell Endocrinol 1989 Aug
PMID:Effects of human chorionic gonadotropin, prostaglandin F2 alpha and protein kinase C activators on the cyclic AMP and inositol phosphate second messenger systems in cultured human granulosa-luteal cells. 255 Feb 98


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