Effect Of LHRH Analog Research Articles

Effects of LHRH-analogues on mitogenic signal transduction in cancer cells

The expression of luteinizing hormone-releasing hormone (LHRH) and its receptors has been demonstrated in a number of human malignant tumors, including cancers of the breast, ovary, endometrium and prostate. These findings suggest the presence of an autocrine regulatory system based on LHRH. Recent studies in our laboratory have demonstrated that the function of LHRH produced by ovarian cancer cells is the inhibition of their proliferation. Dose-dependent antiproliferative effects of LHRH-agonists have been observed by several laboratories in cell lines derived from the above cancers. Interestingly, also LHRH-antagonists have marked antiproliferative activity in most of the ovarian, breast and endometrial cancer cell lines tested so far, indicating that the dichotomy of LHRH-agonists/LHRH-antagonists is not valid for the LHRH-system in cancer cells. In addition, our data suggest that the classical LHRH receptor signal transduction mechanisms known from the pituitary (phospholipase-C, protein kinase C, adenylyl cyclase) are not involved in the mediation of LHRH effects in cancer cells. Data obtained by several groups, including ours, rather suggest that LHRH analogs interfere with the signal transduction of growth-factor receptors and related oncogene products associated with tyrosine-kinase activity. The mechanism of action is probably an LHRH-induced activation of a phosphotyrosine phosphatase, counteracting the effects of receptor associated tyrosine kinase. In our hands, LHRH analogs virtually blocked the EGF-induced MAP-kinase activity of ovarian and endometrial cancer cells. The pharmacological exploitation of this mechanism might provide promising new therapies for these cancers.

Effect of LHRH analog on the seminal vesicles evaluated by transrectal sonography.

The maximum horizontal area (MHA) of the seminal vesicles was measured in 20 prostatic cancer patients by means of transrectal sonography (TRS) after LHRH analog treatment. MHA of the seminal vesicles changed in parallel to the serum testosterone (T) level and decreased by 11-62%, compared with the baseline after LHRH analog treatment for 4 months. Two different patterns were observed for the change of MHA. In 9 cases, MHA of the seminal vesicles increased transiently and then decreased gradually, while in the other 11 cases, MHA decreased continuously from the beginning with no significant increase. Thus, the direct and dynamic response of the seminal vesicles to the change of serum T level was clarified.

LHRH-receptors and LHRH-agonist treatment in ovarian cancer: An overview

Considerable evidence exists that ovarian cancer might be gonadotrophin-dependent. Receptors for LH and FSH have been discovered in these tumors. Proliferation of ovarian cancer cells in vitro could be stimulated by gonadotrophins. Withdrawal of LH and FSH in animal models of ovarian cancer inhibited growth of these tumors. Phase-II clinical studies have shown that suppression of endogenous gonadotrophins by LHRH-agonists can be beneficial in women with advanced ovarian cancer. Respective controlled clinical trials are performed at present. Also direct effects of LHRH analogues on ovarian tumors have been reported. An LHRH like protein was found in human ovarian tissue. We discovered a specific LHRH binding site (mol. wt 63.2 kDa) in ovarian cancer tissue which is very similar to other human extrapituitary LHRH binding sites, of the low-affinity, high-capacity type, e.g. in breast cancer and the placenta. In the latter tissues, LHRH or a related substance has been proposed as an autocrine regulator of cellular function. If this was also the case in ovarian cancer, direct effects of LHRH analogs on the tumor cells could be used as additional therapeutical points of attack.

Effects of LH-RH analogue on LH release and ovarian function in ovarian quiescent heifers.

A total of 10 cases of ovarian quiescent heifers were assigned to 4 treatment groups. Heifers of Group I(n=3), II(n=3), III(n=3) and IV(n=1) were treated with a single intramuscular (IM) injection of 100μg, double IM injections of 100μg at 1 hr interval, single IM injection of 200μg and 400μg of LH-RH analogue, respectively. Changes of LH, estradiol-17β (E2), progesterone (P) levels in peripheral blood and ovarian alteration were examined before and after the treatment. The LH level increased quickly in all cases, reaching a peak of 72.3±42.9 (SD) ng/ml about 2 hr after and returned to a basal level about 7 hr after treatment. There was no significant difference in post-treatment maximum LH levels among Groups I, II and III. Ovulation was induced in 8 cases 35.5±5.3 hr after LH peak. Patterns of ovarian response after treatment were classified into 6 types according to changes of ovarian structure and P and E2 levels. No distinct disparity was found among the 6 types in pre-treatment LH and E2 levels, post-treatment maximum LH levels and amount of released LH, respectively. No correlation between the post-treatment LH release and the succeeding ovarial response was observed.

Effects of LH-RH Analogue on the Ovarian Response and Quality of Embryos in the Japanese Black Cows Superovulated with PMSG and PGF2α

Effects of LH-RH Analogue on the Ovarian Response and Quality of Embryos in the Japanese Black Cows Superovulated with PMSG and PGF<SUB>2</SUB>&alpha;

3 Effects of LH-RH analogues on the testis tissue

3 Effects of LH-RH analogues on the testis tissue

Effects of LH-RH analogue on intratesticular, intratubular, and prostatic tissue androgen livels in prostatic cancer patients

Effects of LH-RH analogue on intratesticular, intratubular, and prostatic tissue androgen livels in prostatic cancer patients

Kinetic evaluation of the effect of LHRH analog on prostatic cancer using transrectal ultrasonotomography.

The size of the prostate was measured in 11 patients with the prostatic cancer by means of transrectal ultrasonotomography after LHRH analog ([Ser(Bu)6] LHRH) treatment. Prostate volume changed parallel to serum testosterone (T) level and decreased by 17-62% compared with baseline after LHRH analog treatment for 4 months. Two different patterns were observed for the change in prostatic volume. Type A expanded transiently and then decreased gradually, while type B decreased continuously from the beginning with no expansion. After treatment for 4 months, the prostatic volume of type A was significantly less than that of type B. It is suggested that prostatic cancer showing a type A regression curve may be more sensitive to T, resulting in a better prognosis than type B.

Direct effects of LHRH analogs on tumor cells

Direct effects of LHRH analogs on tumor cells