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.

EFFECTS OF OESTRADIOL, HYPOTHALAMIC EXTRACTS AND LUTEINIZING HORMONE RELEASING HORMONE ON RAT ANTERIOR PITUITARY GLAND GONADOTROPHIN RELEASE IN VITRO BEFORE AND AFTER THE PREOVULATORY LUTEINIZING HORMONE SURGE AT PRO-OESTRUS

1981 ◽  
Vol 90 (3) ◽  
pp. 345-354 ◽  
Author(s):  
KATHLEEN A. ELIAS ◽  
C. A. BLAKE
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Anterior Pituitary Gland ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Lh Rh ◽  
Lh Releasing Hormone

Changes at the anterior pituitary and/or hypothalamic levels which result in selective FSH release during late pro-oestrus in the cyclic rat were investigated. The possible involvement of decreasing serum concentrations of oestrogen during pro-oestrus in such changes was studied. Rats were decapitated at 12.00 h on pro-oestrus, before the onset of the LH surge and first phase of FSH release, or at 24.00 h on pro-oestrus, shortly after the onset of the second or selective phase of FSH release. Other rats were given oestrogen (OE2) at 14.00 h and killed at 24.00 h pro-oestrus. Paired hemi-anterior pituitary glands were incubated with vehicle or OE2 with or without synthetic LH-releasing hormone (LH-RH) or hypothalamic acid extracts prepared from rats killed at 12.00 or 24.00 h on pro-oestrus. At 24.00 h pro-oestrus, serum FSH concentration was high while serum LH concentration was low regardless of whether rats were given OE2. Glands collected and incubated at 24.00 h released more FSH and less LH than did glands collected and incubated at 12.00 h pro-oestrus. Administration of OE2 in vivo and/or in vitro did not affect these responses. The increments in LH and FSH release attributed to LH-RH or hypothalamic extracts in the glands incubated at 24.00 h were not different from those of the glands incubated at 12.00 h. Also, the hypothalamic extracts prepared from rats killed at 24.00 h were no more effective than the extracts prepared from rats killed at 12.00 h in releasing LH or FSH from glands incubated at 12.00 or 24.00 h pro-oestrus. Administration of OE2 in vivo caused a small suppression of LH-RH-induced FSH release. We suggest that a change occurs at the level of the anterior pituitary gland during the period of the LH surge and first phase of FSH release to increase basal FSH secretion selectively and cause, at least in part, the second phase of increased serum FSH. This change is not mediated by a decrease in serum oestrogen concentration. We failed to observe any evidence that LH-RH causes preferential FSH release during late pro-oestrus or that a hypothalamic peptide with a preferential FSH releasing ability is involved in FSH release at this time.

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.

INHIBITION BY MELATONIN OF THE PITUITARY RESPONSE TO LUTEINIZING HORMONE RELEASING HORMONE IN VIVO

1978 ◽  
Vol 76 (3) ◽  
pp. 487-491 ◽  
Author(s):  
K. YAMASHITA ◽  
M. MIENO ◽  
T. SHIMIZU ◽  
ER. YAMASHITA
Keyword(s):  
Luteinizing Hormone ◽  
Carotid Artery ◽  
Anterior Pituitary ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh ◽  
Lh Secretion

The rate of secretion of 17-oxosteroids by the testes of anaesthetized dogs in vivo was used as an index of LH secretion. Intracarotid injection of luteinizing hormone releasing hormone (LH-RH, 1, 5 or 10 μg/kg body wt) resulted in an increase in the testicular 17-oxosteroid secretion which was roughly proportional to the dose administered and which reached a maximum 60 min after the injection. Testicular output of 17-oxosteroids was unaffected by administration of melatonin (10 or 100 μg/kg body wt) into the carotid artery. When LH-RH (5 μg/kg) was injected into the carotid artery 3 h after intracarotid injection of melatonin (10 or 100 μg/kg), the testicular response to LH-RH was considerably diminished. Pretreatment with melatonin (100 μg/kg) did not alter the testicular response to human chorionic gonadotrophin (20 i.u./kg body wt) given i.v. It is concluded that melatonin may act directly on the anterior pituitary gland in dogs to inhibit the LH-RH-induced release of LH.

Stimulatory effect of thyrotrophin-releasing hormone (TRH) on the release of luteinizing hormone (LH) from rat anterior pituitary cells in vitro

1983 ◽  
Vol 61 (2) ◽  
pp. 186-189 ◽  
Author(s):  
Noboru Fujihara ◽  
Masataka Shiino
Keyword(s):  
Luteinizing Hormone ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells ◽  
Lh Release ◽  
Lh Rh

The effect of thyrotrophin-releasing hormone (TRH, 10−7 M) on luteinizing hormone (LH) release from rat anterior pituitary cells was examined using organ and primary cell culture. The addition of TRH to the culture medium resulted in a slightly enhanced release of LH from the cultured pituitary tissues. However, the amount of LH release stimulated by TRH was not greater than that produced by luteinizing hormone – releasing hormone (LH–RH, 10−7 M). Actinomycin D (2 × 10−5 M) and cycloheximide (10−4 M) had an inhibitory effect on the action of TRH on LH release. The inability of TRH to elicit gonadotrophin release from the anterior pituitary glands in vivo may partly be due to physiological inhibition of its action by other hypothalamic factor(s).

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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