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

1976 ◽  
Vol 71 (1) ◽  
pp. 1-11 ◽  
Author(s):  
G. A. SCHUILING ◽  
H. P. GNODDE

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.

1976 ◽  
Vol 70 (1) ◽  
pp. 97-104 ◽  
Author(s):  
G. A. SCHUILING ◽  
H. P. GNODDE

SUMMARY If long-term ovariectomized rats are treated with the long-acting barbiturate, sodium phenobarbitone, the well-known pulsatile secretion of LH is depressed, resulting in a constant, still raised, plasma LH level. This indicates that in all probability ovariectomized rats secrete LH in both a tonic and a pulsatile way, only the latter being sensitive to phenobarbitone treatment. Constant infusions of synthetic LH-RH into phenobarbitone-treated ovariectomized rats induced a steadily increasing plasma LH concentration without pulsations, whereas pulsatile infusions of the releasing hormone, following a constant infusion, resulted in a pulsatile secretion of LH. This indicates that the pulsatile secretion of LH in ovariectomized rats is the result of a pulsatile secretion of the hypothalamic releasing hormone; the pituitary gland itself is not the site of origin of the phenomenon.


1977 ◽  
Vol 72 (2) ◽  
pp. 121-126 ◽  
Author(s):  
G. A. SCHUILING ◽  
H. P. GNODDE

SUMMARY Oestrogen-induced changes in luteinizing hormone secretion, caused by continuous infusions of luteinizing hormone releasing hormone (LH-RH), appear to depend on the duration of exposure of the pituitary gland to the releasing hormone. The initial oestrogen-induced depression of the potential response of the pituitary gland to LH-RH, which always seems to occur, does not necessarily turn into an enhancement of this potential response. It is suggested that this may be due to the fact that the response of the pituitary gland to LH-RH infusions is a continuously changing parameter influenced by oestrogen.


1977 ◽  
Vol 74 (2) ◽  
pp. 291-296 ◽  
Author(s):  
H. M. FRASER ◽  
J. SANDOW

Immunization against luteinizing hormone releasing hormone (LH-RH) in adult male rats produced a progressive decline in LH and FSH in the circulation to low or non-detectable levels. d-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide is an analogue of LH-RH having highly active LH-RH properties in the normal rat. Because it is also immunologically different from LH-RH it can stimulate gonadotrophin release from the anterior pituitary gland of rats immunized against LH-RH without interference from the antibody. The analogue stimulated LH and FSH release in rats 15 weeks after immunization against LH-RH when antibody titre was highest, and after long-term (35 weeks) immunization against LH-RH. d-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide and related analogues are therefore potentially useful for reversing the effects of immunization against LH-RH.


1974 ◽  
Vol 76 (3) ◽  
pp. 431-437 ◽  
Author(s):  
H. Morishita ◽  
H. Mitani ◽  
Y. Masuda ◽  
K. Higuchi ◽  
M. Tomioka ◽  
...  

ABSTRACT The effect of synthetic luteinizing hormone releasing hormone (LH-RH) on ovulation has been studied during the oestrous cycle in adult female rats. Ovulation could be induced by the administration of 1 μg synthetic LH-RH at 1:00 a. m. on the day of dioestrus II (lights on from 10:00 p.m. to 10:00 a.m.). At 1:00 a.m. on the day of dioestrus II, the average volume of the largest follicles reached a volume of 83 × 106 μm3 and was three fifth of the volume of that at 6:00 a. m. on the day of pro-oestrus (critical period). These findings suggest that the luteinizing hormone (LH) content in the pituitary gland during the early period of dioestrus II is sufficient to induce ovulation and that the follicles that reach to three fifth of the volume at the critical period are capable of ovulating providing endogenous ovulatory LH released.


1979 ◽  
Vol 81 (2) ◽  
pp. 175-182 ◽  
Author(s):  
J. SANDOW ◽  
W. KÖNIG

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.


1982 ◽  
Vol 94 (2) ◽  
pp. 283-287 ◽  
Author(s):  
G. Fink ◽  
W. J. Sheward ◽  
H. M. Charlton

We have investigated the LH response to LH releasing hormone (LH-RH) in female hypogonadal (hpg) mice in which the hypothalamus contains no LH-RH and the pituitary gland contains significantly less LH than in normal mice. Both the releasing action and the priming effect of LH-RH were not significantly different in hpg compared with normal mice. Raised plasma concentrations of oestradiol-17β reduced pituitary responsiveness to LH-RH in normal but not in hpg mice. These results show that in the mouse neither longterm exposure to normal levels of LH-RH nor a normal pituitary content of LH are necessary for either the releasing or the priming action of LH-RH.


1979 ◽  
Vol 80 (1) ◽  
pp. 141-152 ◽  
Author(s):  
A. D. SWIFT ◽  
D. B. CRIGHTON

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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