Prolonged combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and oestradiol benzoate causes long-lasting suppression of the autonomous and the LRH-stimulated secretion of luteinizing hormone and follicle stimulating hormone. An in vitro study

Abstract. The effect of a combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and oestradiol benzoate (EB) on the autonomous and the 'supra-maximally' LRH-stimulated in vitro release of LH and FSH by pituitary glands of 2 weeks ovariectomized (OVX) rats was studied using a perifusion system. The concentration of LRH in the perifusion medium was 1 μg/ml. Pre-treatment with LRH during 6 days was effected by means of sc implanted Alzet® osmotic minipumps (MP). Control rats received a piece of silastic with the dimesions of a minipump ('sham-pump'; Sh-P). EB, 3 μg/injection or solvent (arachis oil) was sc injected on days –3 and –1 (day of perifusion: day 0). Of the pituitary glands of EB-injected, Sh-P-implanted rats both the autonomous and the LRH-stimulated secretion of LH and the LRH-stimulated secretion of FSH were significantly higher than those of the oil-injected, Sh-P-implanted rats without EB administration. Pretreatment with LRH for 6 days had a suppressing effect on the autonomous and the LRH-induced depletion of the pituitary LH and FSH stores. In combination with EB, the suppressing effect of LRH pre-treatment on the LRH-stimulated secretion of LH and FSH was still greater: the pituitary gland appeared to be fixed in a relatively unresponsive state with very low autonomous LH and FSH secretion. It is discussed that increase of pituitary LRH-responsiveness due to EB demands withdrawal of the pituitary gland from the influence of LRH, an effect which is in vivo achieved by the negative feedback of oestrogen on the hypothalamus.

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RELATIVE ACTIVITY, PLASMA ELIMINATION AND TISSUE DEGRADATION OF SYNTHETIC LUTEINIZING HORMONE RELEASING HORMONE AND CERTAIN OF ITS ANALOGUES

Journal of Endocrinology ◽

10.1677/joe.0.0800141 ◽

1979 ◽

Vol 80 (1) ◽

pp. 141-152 ◽

Cited By ~ 40

Author(s):

A. D. SWIFT ◽

D. B. CRIGHTON

Keyword(s):

Luteinizing Hormone ◽

Pituitary Gland ◽

Anterior Pituitary ◽

Inverse Correlation ◽

Anterior Pituitary Gland ◽

Luteinizing Hormone Releasing Hormone ◽

Releasing Hormone ◽

Lh Rh

The abilities of three nonapeptide analogues of synthetic luteinizing hormone releasing hormone (LH-RH) to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in anoestrous and cyclic ewes were examined, as were their elimination from the plasma in vivo and degradation by extracts of the hypothalamus, anterior pituitary gland, lung, kidney, liver and plasma in vitro. In all cases, comparisons were made with synthetic LH-RH. When injected i.v. into mature ewes as a single dose, the potencies of the analogues were graded and Des Gly-NH210 LH-RH ethylamide was found to be the least potent. It was not possible to demonstrate any significant increase in the potency of this analogue over LH-RH, although a trend was apparent with each parameter examined. [d-Ser(But)6] Des Gly-NH210 LH-RH ethylamide had the greatest potency. There were no differences between the responses of anoestrous ewes and those of ewes treated on day 10 of the oestrous cycle. None of the analogues had a rate of elimination from the plasma different from that of LH-RH during either the first or the second components of the biphasic disappearance curve. The incubation of LH-RH with tissue extracts showed that extracts of the hypothalamus and anterior pituitary gland degraded LH-RH to a similar extent. Both the hypothalamic and anterior pituitary gland extracts degraded more LH-RH than did lung extract, which in turn destroyed more LH-RH than did extracts of kidney or liver tissue. The degradative abilities of kidney and liver extracts did not differ from each other. Plasma failed to degrade LH-RH or the analogues. Although LH-RH was rapidly destroyed by hypothalamic extract in vitro, of the analogues, only Des Gly-NH210 LH-RH ethylamide was degraded. The anterior pituitary gland and kidney extracts failed to degrade [d-Ser6] Des Gly-NH210 LH-RH ethylamide and [d-Ser(But)6] Des Gly-NH210 LH-RH ethylamide as rapidly as LH-RH. Extracts of liver and lung were incapable of catabolizing any of the analogues. There was an inverse correlation between the LH- and FSH-releasing potency of an analogue and its rate of degradation by anterior pituitary gland extract. The slower rates of catabolism of certain analogues of LH-RH by the anterior pituitary gland may explain their increased LH- and FSH-releasing potency.

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Desensitization of the pituitary gland induced in vivo by luteinizing hormone-releasing hormone (LRH) or by the LRH-analogue buserelin does not affect the autonomous secretion of luteinizing hormone and follicle stimulating hormone as observed in vitro

Acta Endocrinologica ◽

10.1530/acta.0.1060454 ◽

1984 ◽

Vol 106 (4) ◽

pp. 454-458 ◽

Cited By ~ 4

Author(s):

G. A. Schuiling ◽

H. Moes ◽

T. R. Koiter

Keyword(s):

Luteinizing Hormone ◽

Pituitary Gland ◽

Normal Level ◽

Ovariectomized Rats ◽

Complete Suppression ◽

Pituitary Glands ◽

Pre Treatment ◽

Lh Secretion

Abstract. Three-weeks ovariectomized rats were sc implanted with Alzet® osmotic minipumps which released either LRH or the LRH-analogue buserelin at the rate of 250 ng/h. Control rats were implanted with a silastic 'shampump'. After explantation, 6 days later, the pituitary glands of part of these rats were exposed to the maximally active LRH concentration of 1 μg/ml for a period of 6 h. using a perifusion system. In a second group of rats explantation and perifusion was done not directly, but 5 days after cessation of the I.RH pretreatment. After 6 days in vivo pre-treatment with LRH or with buserelin the pituitary LH and FSH stores were partially depleted, the depletion after buserelin being stronger than after LRH. The pituitary glands of the first group of rats showed rates of both maximally LRH-stimulated and unstimulated (autonomous) LH- and FSH-secretion which were strongly impaired, the impairment after buserelin being stronger than after LRH. In the group with a 5 days interval between in vivo LRH/buserelin pre-treatment and explantation the pituitary LH and FSH stores were restored to the range of pre-treatment levels. Of these pituitaries the autonomous secretion of LH and FSH as well as the maximally LRH-stimulated secretion of FSH was restored to the normal level; the maximally LRH-stimulated secretion of LH, however, remained depressed, indicating that 5 days after cessation of exposure to LRH or to buserelin, and in spite of restored pituitary LH/FSH contents, the sensitivity of the LH releasing system to LRH was still subnormal. The results suggest that the autonomous secretion of LH and FSH as well as the LRH-stimulated secretion of FSH, but not the LRH-stimulated secretion of LH may be dependent on the content of the pituitary LH and FSH stores. Furthermore, after treatment with LRH or buserelin the autonomous secretion of LH may return to a normal level when the sensitivity of the LH releasing system to LRH is still impaired: apparently, the mechanisms underlying the autonomous and the LRH-stimulated LH secretion do not influence each other. It is discussed that in situations in which a complete suppression of the pituitary-gonadal axis is demanded (carcinomata of the breast or the prostate; precocious puberty) desensitization of the pituitary gland with super-active LRH-analogues like buserelin alone is not sufficient, as this does not affect the autonomous secretion of LH and FSH. For total suppression of gonadal activity the pituitary gland must be completely depleted with relatively large doses of analogue.

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In Vitro Release of Luteinizing Hormone-Releasing Hormone

Hormonally Active Brain Peptides ◽

10.1007/978-1-4615-9248-8_7 ◽

1982 ◽

pp. 125-140

Author(s):

E. J. Peck ◽

C. Pasqualini ◽

B. Kerdelhué

Keyword(s):

Luteinizing Hormone ◽

In Vitro Release ◽

Luteinizing Hormone Releasing Hormone ◽

Releasing Hormone ◽

Vitro Release

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SECRETION OF LUTEINIZING HORMONE CAUSED BY CONTINUOUS INFUSIONS OF LUTEINIZING HORMONE RELEASING HORMONE IN THE LONG-TERM OVARIECTOMIZED RAT: EFFECT OF OESTROGEN PRETREATMENT

Journal of Endocrinology ◽

10.1677/joe.0.0710001 ◽

1976 ◽

Vol 71 (1) ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

G. A. SCHUILING ◽

H. P. GNODDE

Keyword(s):

Luteinizing Hormone ◽

Pituitary Gland ◽

Ovariectomized Rats ◽

Luteinizing Hormone Releasing Hormone ◽

Releasing Hormone ◽

Clear Cut ◽

Oestradiol Benzoate ◽

Maximal Plasma ◽

Lh Rh

SUMMARY Continuous infusions of luteinizing hormone releasing hormone (LH-RH) into phenobarbitone-treated long-term ovariectomized rats, resulted in patterns of LH secretion which were determined by the blood LH-RH concentration. Infusions of 52 ng LH-RH/h caused steadily increasing plasma LH levels, which stabilized after about 2 h of infusion and were maintained for the rest of the experiment (9 h). A similar course of plasma LH concentration was observed as a result of infusions of 104 ng LH-RH/h, though in this case LH concentrations reached higher levels than those induced by infusion of 52 ng LH-RH/h. Higher rates of LH-RH infusion (208 and 416 ng/h), however, induced clear-cut LH peaks, which reached their maximal plasma values after 2–3 h of infusion and then declined again until, at the end of the experiment, they were only slightly higher than the LH levels induced by infusions of 52 ng LH-RH/h. A similar series of LH-RH infusions given to ovariectomized rats pretreated with oestradiol benzoate during 3 days (the rats were injected daily with 7 μg steroid), produced a highly augmented response of the pituitary gland, but all LH-RH concentrations infused induced rather sharp LH peaks, reaching their maximum after 2–3 h of infusion. After 5 h of infusion the descending parts of all these peaks appeared to converge. In both control and oestradiol benzoate-pretreated rats there appeared to be a linear relationship between the logarithm of the blood LH-RH concentration and the maximal plasma LH values on one hand, and the amount of LH secreted during the first 5 h of infusion on the other. Furthermore, it appeared that the longer the period of oestrogen action, the more the response of the pituitary gland to a certain dose of LH-RH was enhanced.

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