1.Effect of treatment with LHRH analogs containing cytotoxic radicals on the binding characteristics of receptors for luteinizing-hormone-releasing hormone in MXT mouse mammary carcinoma.
Milovanovic SR1, Monje E, Szepeshazi K, Radulovic S, Schally A. J Cancer Res Clin Oncol. 1993;119(5):273-8.
Binding capacities and apparent dissociation constants of receptors for luteinizing-hormone-releasing hormone (LHRH) were investigated in estrogen-independent MXT mammary cancers of untreated mice and after in vivo treatment with agonistic or antagonistic analogs of LHRH containing cytotoxic radicals: AJ-04 (agonist [D-Lys6]LHRH linked to methotrexate), T-98-([D-Lys6]LHRH coupled to glutaryl-2-(hydroxmethyl)anthraquinone (G-HMAQ)) and T-121/B (LHRH antagonist T-147 containing two residues of G-HMAQ), which induced tumor growth inhibition. The effects were compared to LHRH agonist [D-Trp6]LHRH and carriers [D-Lys6]LHRH, LHRH antagonist T-147, as well as to methotrexate, G-HMAQ and surgical bilateral overiectomy. Analysis of the binding data revealed that in control tumors the interaction of 125I-[D-TRP6]LHRH was consistent with the presence of one class of saturable, specific, noncooperative, high-affinity and low-capacity binding sites. Chronic treatment of mice bearing MXT tumors with LHRH analogs AJ-04 and T-121/B carrying cytotoxic radicals, but not with T-98 produced significant down-regulation of membrane receptors for LHRH.
2.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.
Simard J1, Labrie C, Hubert JF, Labrie F. Mol Endocrinol. 1988 Sep;2(9):775-84.
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.
3.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.
Hubert JF1, Simard J, Gagné B, Barden N, Labrie F. Mol Endocrinol. 1988 Jun;2(6):521-7.
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.
