Mechanism of Action of Luteinizing Hormone Releasing Hormone and Thyrotropin Releasing Hormone in the Anterior Pituitary Gland and Modulation of their Activity by Peripheral Hormones

1977 ◽  
pp. 157-179 ◽  
Author(s):  
Fernand Labrie ◽  
Jacques Drouin ◽  
André De Léan ◽  
Lisette Lagacé ◽  
Louise Ferland ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Mechanism Of Action ◽  
Anterior Pituitary ◽  
Thyrotropin Releasing Hormone ◽  
Anterior Pituitary Gland ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone

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

1979 ◽  
Vol 80 (1) ◽  
pp. 141-152 ◽  
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.

ONTOGENY OF THE SENSITIZING EFFECT OF OESTRADIOL AND LUTEINIZING HORMONE RELEASING HORMONE ON THE ANTERIOR PITUITARY GLAND OF THE FEMALE RAT

1981 ◽  
Vol 91 (2) ◽  
pp. 347-351 ◽  
Author(s):  
R. MEIDAN ◽  
G. FINK ◽  
Y. KOCH
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Priming Effect ◽  
Anterior Pituitary Gland ◽  
Female Rats ◽  
Facilitatory Effect ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh

The ontogeny of the facilitatory effect of oestradiol and luteinizing hormone releasing hormone (LH-RH) on the responsiveness of the anterior pituitary gland to LH-RH has been studied in vitro using pituitary glands from female rats aged 15, 17, 20, 31, 35 and 38 days. The facilitatory effect of oestradiol was already well established by day 15, while the facilitatory effect of LH-RH (priming effect) developed only after day 17. Although it increased the overall response of the gland to LH-RH, oestradiol did not selectively enhance the priming effect of LH-RH. Both the effect of oestradiol and LH-RH reached a peak on day 25, 7 days before vaginal opening in this colony, and, as assessed by measuring pituitary LH contents, were not dependent upon the synthesis of LH. These data show that different mechanisms may be involved in the facilitation of pituitary responsiveness by oestradiol and LH-RH, but that both mechanisms appear to depend more upon an increase in the sensitivity of the receptor/release apparatus rather than in the gonadotrophin content of the gonadotrophs.

STUDIES WITH FRAGMENTS OF A HIGHLY ACTIVE ANALOGUE OF LUTEINIZING HORMONE RELEASING HORMONE

1979 ◽  
Vol 81 (2) ◽  
pp. 175-182 ◽  
Author(s):  
J. SANDOW ◽  
W. KÖNIG
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Enzyme Stability ◽  
Organ Distribution ◽  
Structural Requirements ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Highly Active ◽  
Lh Rh

The minimal structural requirements for gonadotrophin releasing activity were studied with fragments of a highly active analogue of luteinizing hormone releasing hormone (LH-RH), [d-Ser(But)6]LH-RH(1–9)nonapeptide-ethylamide (Hoe 766). All fragments are related to the C-terminal structure of LH-RH and have increased enzyme stability. Ovulation in phenobarbitone-blocked rats was induced with a median effective dose/rat, of 1·9 μg of the (3–9)-heptapeptide, Trp-Ser-Tyr-d-Ser(But)-Leu-Arg-Pro-ethylamide and 6·8, 18·0 and 38·3 μg for the (4–9), (5–9) and (6–9) fragments respectively. The (3–9)-heptapeptide and (4–9)-hexapeptide induced release of LH and FSH in phenobarbitone-blocked rats with a ratio similar to that of LH-RH. Degradation of LH-RH by enzyme preparations of liver, kidney and hypothalamic or anterior pituitary tissue was not modified by addition of the (3–9)-heptapeptide fragment. The organ distribution of the 125I-labelled (3–9)-heptapeptide fragments was similar to LH-RH, but not to Hoe 766. The peptide accumulated in liver and kidney, but was eliminated from the anterior pituitary gland 15 min after i.v. injection, whereas Hoe 766 showed progressive accumulation in the pituitary gland (tissue: plasma ratio = 6·6 after 60 min). In contrast to C-terminal fragments of LH-RH, the corresponding fragments of nonapeptide analogues retained significant biological activity, and the minimal structural requirements for LH release may be related to the C-terminal sequence of LH-RH.

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