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Biomedical subjects

F Labrie

Publications and source records attributed to F Labrie.

At least 541 records · Page 30Linked to original sources
PubMed1981

Effect of an LHRH analog on growth and hormone receptor levels in DMBA-induced mammary tumors in the rat.

Dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in the rat are well known to be hormono-dependent. Daily injections of an LHRH agonist, [D-Ala6, des-Gly-NH2(10)]LHRH ethylamide (LHRH-A), 1 microgram daily, for 38 days results in a 35% decrease in the number of tumors present at the beginning of the experiment compared to a decline of 45% after ovariectomy and of 8% in the control group. This is accompanied by a marked reduction in ovarian LH and FSH receptors. LHRH-A treatment also resulted in reduction in the number of progesterone and prolactin receptors in the tumors. In addition, an increase in plasma LH and FSH and a decline in plasma prolactin (PRL) concentrations are observed. The mechanisms by which the LHRH agonist induces its antitumoral effect probably relate to an ovarian desensitization to LH and FSH with a concomitant decrease in circulating levels of estrogen and prolactin, two well known stimuli for the growth of DMBA-induced mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Increased testicular 5 alpha-androstane-3 alpha, 17 beta-diol formation induced by treatment with [D-Ser (TBU) 6, des-Gly-NH2(10)] LHRH ethylamide in the rat.

While the intact male adult rats respond to LH with a predominant increase of testicular and plasma testosterone levels, the response to LH stimulation in animals treated with the LHRH agonist, [D-Ser(TBU) 6, des-Gly-NH2(10)] LHRH ethylamide is characterized by a major production of 5 alpha-androstane-3 alpha, 17 beta-diol. The marked increase of 5 alpha-androstane-3 alpha, 17 beta-diol levels in the presence of a 90% decrease of testosterone concentration strongly suggests that 5 alpha-reductase and 3 alpha-hydroxysteroid oxidoreductase activities are increased during testicular desensitization induced by treatment with the LHRH agonist.

3-Hydroxysteroid Dehydrogenases↗
PubMed1980

Impairment of pituitary and gonadal functions in alloxan-induced diabetic male rats.

The inhibitory effect of treatment with a potent LHRH agonist on testicular gonadotropin-receptor levels was compared in intact and diabetic rats. Basal and LHRH-induced pituitary gonadotropin secretion as well as the testicular steroidogenic response to oLH were assessed. A single injection of alloxan (65 mg/kg) led, after 6 weeks, to a 40% decrease of testicular LH- and prolactin-receptor levels. Treatment for 2 weeks with [D-Ala6,des-Gly-NH 1/2 0] LHRH ethylamide (100 ng every second day) led to a 70% reduction of LH-receptor levels accompanied by decreased testicular weight, a similar inhibition being found in intact and diabetic animals. Seminal vesicle and ventral prostate weight were markedly reduced in diabetic animals, a further decrease being obtained after treatment with the LHRH agonist. The loss of accessory sex-organ weight in alloxan-diabetic rats was accompanied by a reduction in the basal testicular content of pregnenolone, progesterone, 17-OH-progesterone, androstenedione, testosterone and dihydrotestosterone whereas the steroid response to oLH was within normal limits. We next examined the possible changes of LH and FSH secretion which could be responsible for the reduced testicular function in diabetic animals. Basal plasma-LH levels were 30% reduced in rats 6 weeks after treatment with alloxan while basal plasma-FSH levels remained unchanged. When the pituitary gonadotropin response to LHRH was measured in chronically cannulated freely-moving intact and diabetic rats, an approx. 50% inhibition of the LH and FSH responses to LHRH was observed in diabetic animals.

Alloxan↗
PubMed1980

Specific binding of a potent LHRH agonist in rat testis.

High affinity binding sites for the potent LHRH agonist [125I][D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide are present in dissociated rat testicular interstitial cells, a preparation rich in Leydig cells. The iodinated LHRH agonist binds to a single class of high affinity sites at a KD value of 0.12 nM and the number of binding sites is approx. 2500 per interstitial cell. A close correlation is observed between the potency of representative LHRH agonist to stimulate LH release in anterior pituitary cells in culture and their affinity for the testicular binding sites. The presence of specific LHRH receptors in an enriched population of Leydig cells suggests that these receptors could play a role, not only in the antifertility effects of LHRH agonists, but also in the physiological control of testicular functions.

Animals↗
PubMed1980

Effects of RU16117, an orally active weak oestrogenic compound, in postmenopausal women.

Daily oral administration of 1, 3 or 10 mg of RU16117 (11 alpha-methoxy ethinyl oestradiol) to normal postmenopausal women led to a progressive decrease of basal serum LH levels to 60.4 +/- 17.0, 35.1 +/- 9.1 and 20.1 +/- 2.8% of control (pretreatment values, P less than 0.01), respectively, after 4 wk of drug administration. Although the pattern was similar, the inhibitory effect of RU16117 was even more pronounced on FSH than LH levels: a 50% decrease of basal LH and FSH levels was obtained at the daily 1.8 and 1.2 mg doses of RU16117, respectively. No significant change of basal serum gonadotrophin levels was observed with the daily 0.3 mg dose. Administration of 1 mg of RU16117 every second day or 10 mg once a week led to a relatively small but significant (P less than 0.05) 20--25% decrease of basal serum LH levels after 4 wk of treatment in four out of five women. While daily 0.3 and 1.0 mg doses of RU16117 had no significant effect on the LH response to 100 microgram LHRH, the 3.0 mg dose delayed the response up to 90 min. The 10 mg dose, on the other hand, led to a markedly delayed and reduced response. Treatment for the same period (4 wk) with 1 mg RU16117 every second day or 10 mg once a week led to a small (20--25%, P less than 0.05) inhibition of the LH response to LHRH. At the dose of 10 mg once a week, RU16117 had no or minimal effect on endometrial histology. Since RU16117, an orally active weak oestrogenic compound, has been shown to have anticarcinogenic activity in the rat, the present findings suggest that this new steroid could be useful for the treatment of climacteric symptoms.

Aged↗
PubMed1980

Inhibition of progesterone secretion during the luteal phase by two luteinizing hormone-releasing hormone agonists in Macaca fascicularis.

The administration of 200 microgram of the potent luteinizing hormone-releasing hormone (LHRH) agonist [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide on day 6 following the plasma estradiol peak to 11 female monkeys (Macaca fascicularis) during two consecutive menstrual cycles decreased plasma progesterone levels by 40.0% +/- 3.9% as compared with previous control cycles. The plasma estradiol profile and the cycle length were not affected significantly by the treatment. Similar results were obtained with 25 microgram of [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide administered to one monkey at the same period of the cycle, such treatment leading to a 41% inhibition of circulating progesterone levels. Although plasma progesterone levels were still reduced in the two post-treatment cycles in monkeys treated with the high dose (200 microgram) of [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide, the recovery cycle was normal after the administration of a lower dose (25 microgram) of [D-Ser(TBU)6, des-Gly-NH2(10)] LHRH ethylamide. The M. fascicularis monkey thus appears as a valid model with which to study the inhibitory effects of LHRH agonists on luteal function.

Animals↗
PubMed1980

Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary.

To study the luteinizing hormone-releasing hormone (LH-RH; luliberin) receptors in the rat anterior pituitary gland and ovary, 125I-labeled [D-Ser(TBU)6des-Gly-NH2(10)]LH-RH ethylamide was used as a labeled ligand. The binding characteristics were assessed by Scatchard analysis of labeled ligand binding and by potency displacement with unlabeled peptides. Similar Kd values, ranging from 0.1 to 0.3 nM, were found for the labeled and unlabeled peptides in both tissues. A similar order of potency was observed between the finding affinity of 15 peptides in anterior pituitary and ovarian homogenates and their biological activity on luteinizing hormone release in rat anterior pituitary cells in culture. These data demonstrate that the LH-RH receptors present in the rat ovary have a specificity similar to that of the anterior pituitary LH-RH receptor controlling secretion of luteinizing hormone and follicle-stimulating hormone. Moreover, the binding affinities of the LH-RH agonists and antagonists can account, at least up to a large extent, for their relative biological potencies. Although there definitely are specific LH-RH receptors in the ovary which may play a role in the antifertility effects observed after administration of LH-RH agonists, the possible physiological significance of these ovarian receptors is still unknown and of great biological interest.

Animals↗