SITE OF ORIGIN OF THE PULSATILE SECRETION OF LUTEINIZING HORMONE IN LONG-TERM OVARIECTOMIZED RATS

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.

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.


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.


1981 ◽  
Vol 88 (1) ◽  
pp. 17-25 ◽  
Author(s):  
E. M. CONVEY ◽  
J. S. KESNER ◽  
V. PADMANABHAN ◽  
T. D. CARRUTHERS ◽  
T. W. BECK

In ovariectomized heifers, oestradiol decreases concentrations of LH in serum for approximately 12 h after which LH is released in a surge comparable in size and duration to the preovulatory surge. Using this model, we measured LH release induced by LH releasing hormone (LH-RH) from pituitary explants taken from ovariectomized heifers before or after an oestradiol-induced LH surge. These changes were related to changes in LH concentrations in serum and pituitary glands and hypothalamic LH-RH content. Twenty Holstein heifers were randomly assigned to one of four treatment groups to be killed 0, 6, 12, or 24 h after the injection of 500 μg oestradiol-17β. Jugular blood was collected at −2, −1 and 0 h then at intervals of 2 h until slaughter. Pituitary glands were collected and ≃2 mm3 explants were exposed to 4 ng LH-RH/ml medium for 30 min (superfusion) or 4 ng LH-RH/ml medium for 2 h in Erlenmeyer flasks. Levels of LH were measured in the medium. Hypothalami, collected at autopsy, were assayed for LH-RH content. To determine pituitary LH content, an additional 15 ovariectomized heifers were killed, five each at 0, 12 and 24 h after the injection of 500 μg oestradiol. In both groups of heifers, oestradiol reduced serum LH concentrations to ≃ 1 ng/ml, a level which persisted for 12 h, when LH was released in a surge. Pituitary sensitivity to LH-RH was increased at 6 and 12 h after the injection of oestradiol, but was markedly decreased at 24 h, i.e. after the LH surge. Despite this twofold increase in capacity of the pituitary gland to release LH in response to LH-RH, pituitary LH content did not change during 12 h after oestradiol treatment. However, LH content decreased after the LH surge and this decrease was associated with a decrease in pituitary responsiveness to LH-RH. Hypothalamic LH-RH content was not altered by these treatments. We have interpreted our results as evidence that oestradiol exerts a positive feedback effect on the pituitary gland of ovariectomized heifers such that pituitary sensitivity to LH-RH is increased twofold by the time the LH surge is initiated. In addition, oestradiol causes a transitory inhibition of LH-RH release as shown by the fact that serum LH concentrations remained low during the interval from injection of oestradiol until the beginning of the LH surge despite the fact that pituitary sensitivity to LH-RH is increased at this time. Depletion of a readily releasable pool of pituitary LH may be the mechanism by which the LH surge is terminated.


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.


1979 ◽  
Vol 91 (3) ◽  
pp. 577-590 ◽  
Author(s):  
H. Vierhapper ◽  
W. Waldhäusl ◽  
P. Nowotny

ABSTRACT D-Ser-(TBU)6-EA10-LH-RH, an analogue of luteinizing hormone-releasing hormone (LH-RH) with prolonged action evokes in normal male and female subjects a qualitatively different secretory pattern of LH, as peak levels are reached between 30 and 60 min in males and between 120 and 240 min in females. Females with increased production of adrenal androgens due to congenital adrenal hyperplasia (off substitution therapy; N = 8), idiopathic hirsutism (N = 1) and adrenocortical carcinoma (N = 2) present upon the administration of the LH-RH-analogue with a secretory pattern of LH and FSH which is qualitatively identical with that of normal female subjects, whereas the response of LH in these patients differs from that seen in normal males. Pre-treatment with dexamethasone did not induce any qualitative changes in the secretory response of LH and FSH upon the LH-RH-analogue in patients with increased endogenous production of adrenal androgens. A larger pool and/or a more pronounced de novosynthesis of LH, which apparently is not altered by increased levels of adrenal androgens, may be the cause of the more pronounced and prolonged increase of LH in female subjects following the administration of the LH-RH-analogue.


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