Effects of a single injection of a new depot formulation of an LH-releasing hormone agonist on spermatogenesis in adult rats

1986 ◽  
Vol 111 (3) ◽  
pp. 449-NP ◽  
Author(s):  
M. J. P. G. van Kroonenburgh ◽  
J. L. Beck ◽  
H. M. Vemer ◽  
R. Rolland ◽  
C. M. G. Thomas ◽  
...  
Keyword(s):  
Single Injection ◽  
Flow Cytometric Analysis ◽  
Maximum Effect ◽  
Testis Weight ◽  
Depot Formulation ◽  
Releasing Hormone ◽  
Lhrh Analogue ◽  
Essentially Normal ◽  
Lh Rh ◽  
Lh Releasing Hormone

ABSTRACT Adult male Wistar rats were treated with a single injection (500 μg s.c.) of a new biodegradable depot formulation of the LH-releasing hormone (LHRH) analogue [d-Ser(But)6]AzGly10-LH-RH (Zoladex; ICI 118 630) to evaluate its potential for inhibiting spermatogenesis. The drug produced a marked (P≤0·05) decrease in serum concentrations of FSH, LH and testosterone with a maximum effect 14 days after treatment. Since striking focal histological changes were seen in the testis after only 1 week, at a time when changes in serum gonadotrophins were minimal, there may be a direct effect of the LHRH analogue on spermatogenesis. Degenerative changes in germ cells as well as Sertoli cells could be observed. Flow-cytometric analysis of testicular cell suspensions showed a significant decline in the absolute numbers of haploid cells (spermatids), tetraploid cells (mainly pachytene spermatocytes) and of the numbers of cells in the S-phase of the cell cycle. This suggests that the drug also inhibits proliferation of spermatogonia and/or primary spermatocytes. Testis weight, serum hormone concentrations, and histological and cytological parameters returned to essentially normal values 52 days after the injection. It is concluded that this new method of administration may have practical and pharmacokinetic advantages for the purpose of reversible inhibition of spermatogenesis. J. Endocr. (1986) 111, 449–454

EFFECT OF CORTISOL OR ADRENOCORTICOTROPHIN ON RELEASE OF LUTEINIZING HORMONE INDUCED BY LUTEINIZING HORMONE RELEASING HORMONE IN THE DAIRY HEIFER

1982 ◽  
Vol 92 (1) ◽  
pp. 141-146 ◽  
Author(s):  
R. L. MATTERI ◽  
G. P. MOBERG
Keyword(s):  
Luteinizing Hormone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Dairy Heifers ◽  
Significant Difference ◽  
Significant Depression ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
And Control ◽  
Slight Depression

During treatment with cortisol or ACTH, dairy heifers were given two doses of LH releasing hormone (LH-RH) spaced 1·5 h apart. Serum concentrations of cortisol and LH were monitored during each treatment. Treatment with both ACTH and cortisol raised plasma cortisol levels above the respective saline controls (P<0·001). Neither treatment affected basal LH concentrations. A slight depression in LH response was seen in the cortisol-treated animals after the first LH-RH injection, as shown by a statistically significant depression at three of the sample times. There was no significant difference between treated and control LH values after the second LH-RH administration. Treatment with ACTH resulted in significantly reduced LH values at all sample times after both injections of LH-RH.

Studies on the mechanism of the selective suppression of plasma levels of follicle-stimulating hormone in the female rat after administration of steroid-free bovine follicular fluid

1983 ◽  
Vol 97 (3) ◽  
pp. 327-338 ◽  
Author(s):  
W. J. de Greef ◽  
F. H. de Jong ◽  
J. de Koning ◽  
J. Steenbergen ◽  
P. D. M. van der Vaart
Keyword(s):  
Follicular Fluid ◽  
Plasma Levels ◽  
Single Injection ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Female Rat ◽  
Clearance Rates ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Hypophysial Portal

Steroid-free bovine follicular fluid (bFF) selectively suppresses the plasma levels of FSH in the female rat, demonstrating that bFF contains inhibin-like material. The present study was concerned with the effects of bFF on the hypothalamic release of LH releasing hormone (LH-RH) into hypophysial stalk blood and on the metabolic clearance rates of gonadotrophins. The metabolic clearance rates of FSH, LH and prolactin were determined after a single injection of and during a constant infusion with adenohypophysial extract. Similar results were obtained with both methods, and treatment with bFF did not alter the metabolic clearance rates of FSH, LH and prolactin. Anaesthesia with urethane, used for surgery involved in the collection of hypophysial stalk blood, did not interfere with the effect of bFF on plasma levels of FSH. The administration of bFF did not change the hypothalamic content of LH-RH, but caused a 30% decrease in the levels of LH-RH in hypophysial stalk plasma. However, a fraction isolated from bFF, which contained 20 times more inhibin-like activity per mg protein than bFF, did not alter the hypothalamic release of LH-RH into the hypophysial portal blood while this fraction was effective in specifically suppressing the plasma levels of FSH. It was concluded that the inhibin-like activity in bFF does not suppress the plasma levels of FSH by affecting its plasma clearance or by influencing the hypothalamic release of LH-RH, but that it has a direct effect on the adenohypophysis in inhibiting the release of FSH. Besides the inhibin-like activity, bFF also contains another factor which can decrease the levels of LH-RH in hypophysial stalk plasma.

Relative Insensitivity of Rhesus Monkeys to the LH-Releasing Hormone (LH-RH)

1973 ◽  
Vol 36 (2) ◽  
pp. 372-374 ◽  
Author(s):  
AKIRA ARIMURA ◽  
HAROLD G. SPIES ◽  
ANDREW V. SCHALLY
Keyword(s):  
Rhesus Monkeys ◽  
Releasing Hormone ◽  
Lh Rh ◽  
Lh Releasing Hormone

DIAGNOSTIC VALUE OF THE LH-RELEASING HORMONE STIMULATION TEST IN FUNCTIONAL AMENORRHEA

1975 ◽  
Vol 78 (4) ◽  
pp. 625-633 ◽  
Author(s):  
D. Vandekerckhove ◽  
M. Dhont ◽  
J. Van Eyck
Keyword(s):  
Anorexia Nervosa ◽  
Diagnostic Value ◽  
Base Line ◽  
List Type ◽  
Releasing Hormone ◽  
The Absolute ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Circulating Levels ◽  
Secretory Capacity

ABSTRACT LH-releasing hormone (25 μg, iv.) was administered to 37 women with functional amenorrhea. In addition to the clinical classification, these patients were divided into three groups according to the basal level of serum LH. A significant correlation was found between the base-line levels of LH and the serum concentration of oestradiol plus oestrone. The absolute increment of LH after the injection of LH-RH was found to be dependent only on the base-line level of LH. Except for the patients with anorexia nervosa, the base-line levels and the response pattern of FSH were almost the same for all three groups. From the results of this study, it was concluded that: The circulating levels of oestradiol and oestrone, where derived from ovarian secretion, actually depend on the gonadotrophic stimulus. In patients with functional amenorrhea, the oestrogens do not make an independent contribution to the pituitary response to LH-RH. Dysregulation of releasing hormones, whether located at the hypothalamic or suprahypothalamic level, necessarily influences the secretory capacity of the pituitary gland; long-standing deficiency of LH-RH may finally lead to a state of pituitary "functional" unresponsiveness to releasing hormones. In view of the excellent correlation between the base-line levels of LH and the absolute increment of LH following stimulation with LH-RH, this test only accentuates the existing pituitary secretory capacity, which can be roughly estimated from the circulating levels of LH and FSH. This test may be useful in distinguishing the milder cases of psychogenic amenorrhea from extreme gonadotrophic dysfunction in patients with anorexia nervosa.

scholarly journals Studies on the Measurements of LH-releasing Hormone (LH-RH) by Radioimmunoassay (RIA)

1976 ◽  
Vol 52 (1) ◽  
pp. 62-71
Author(s):  
Takayuki KTNUGASA ◽  
Osamu TANIZAWA ◽  
Kenji YAMAJI ◽  
Keiichi KURACHI
Keyword(s):  
Releasing Hormone ◽  
Lh Rh ◽  
Lh Releasing Hormone

LUTEINIZING HORMONE RELEASING HORMONE-INDUCED RELEASE OF LUTEINIZING HORMONE FROM PITUITARY EXPLANTS OF COWS KILLED BEFORE OR AFTER OESTRADIOL TREATMENT

1981 ◽  
Vol 88 (1) ◽  
pp. 17-25 ◽  
Author(s):  
E. M. CONVEY ◽  
J. S. KESNER ◽  
V. PADMANABHAN ◽  
T. D. CARRUTHERS ◽  
T. W. BECK
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Oestradiol Treatment ◽  
Readily Releasable Pool ◽  
Serum Lh ◽  
Pituitary Glands ◽  
Lh Rh ◽  
Lh Releasing Hormone

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.

THE ANTIGENIC DETERMINANT OF THE LH-RELEASING HORMONE FOR THREE DIFFERENT ANTISERA

1975 ◽  
Vol 78 (1) ◽  
pp. 222-231 ◽  
Author(s):  
A. Arimura ◽  
H. Sato ◽  
D. H. Coy ◽  
R. B. Worobec ◽  
A. V. Schally ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Rabbit Antiserum ◽  
Cross Reactivity ◽  
Amide Group ◽  
Antigenic Determinants ◽  
Releasing Hormone ◽  
C Terminus ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Antigen Antibody

ABSTRACT Antigenic determinants of LH-releasing hormone (LH-RH) were investigated by testing the cross-reaction of LH-RH analogues and fragments in LH-RH radioimmunoassay (RIA) systems using 3 different antisera against the LH-RH decapeptide. Rabbit antiserum No. 419 was generated against LH-RH adsorbed on polyvinylpyrrolidone (PVP). Antisera Nos. 710 and 742 were produced by immunizing rabbits with LH-RH conjugated either with bovine serum albumin through its C-terminus, or with human serum albumin through the N-terminus, respectively. For antiserum No. 419, the N-terminal (pyro)-glutamic acid and/or histidine in positions 1 and 2 of LH-RH, respectively, were found to enhance the antigen-antibody interaction, but were not indispensable for it. Similarly, the C-terminal amide and glycine-NH2 did not play a major role in these interactions. The LH-RH heptapeptide fragment, corresponding to amino acid sequence from positions 3 to 9, showed a cross-reactivity in this RIA system with LH-RH, although greater amounts than those of cold LH-RH were required for a comparable inhibition of binding of labelled LH-RH. For antiserum No. 710, the LH-RH hexapeptide fragment corresponding to positions 2 to 7 showed considerable cross-reac tivity. Histidine in position 2 played an important role but neither the amide group nor the glycine amide group at the C-terminus were essential. For antiserum No. 742, the C-terminal tetrapeptide-amide fragment of LH-RH showed considerable cross-reactivity in the LH-RH, the amide moiety itself being of crucial importance. These antisera may be useful in investigating peptides related to LH-RH in biological materials.

Production of Antiserum to LH-Releasing Hormone (LH-RH) Associated with Gonadal Atrophy in Rabbits: Development of Radioimmunoassays for LH-RH

Endocrinology ◽  
1973 ◽  
Vol 93 (5) ◽  
pp. 1092-1103 ◽  
Author(s):  
A. ARIMURA ◽  
H. SATO ◽  
T. KUMASAKA ◽  
R.B.fun WOROBEC ◽  
L. DEBELJUK ◽  
...  
Keyword(s):  
Releasing Hormone ◽  
Gonadal Atrophy ◽  
Lh Rh ◽  
Lh Releasing Hormone

CIRCULATING LUTEINIZING HORMONE AND TESTOSTERONE RESPONSE IN RAMS AFTER LUTEINIZING HORMONE RELEASING HORMONE TREATMENT

1974 ◽  
Vol 77 (1) ◽  
pp. 1-9 ◽  
Author(s):  
D. B. Galloway ◽  
Y. Cotta ◽  
J. Pelletier ◽  
M. Terqui
Keyword(s):  
Luteinizing Hormone ◽  
Single Injection ◽  
Hormone Treatment ◽  
Injection Level ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Positive Correlation ◽  
Quantitative Manner ◽  
Lh Rh ◽  
The Relationship

ABSTRACT The relationship between the secretions of LH and testosterone after LH-RH administration was tested in entire rams. Three groups of two rams received, intravenously, 100 μg; 800 μg LH-RH in single injection; or 100 μg × 7 injections at half-hour intervals respectively and samples were collected every 10 or 20 min for 6 hours. Plasma LH and testosterone were assayed by radioimmunoassay. The quantity of LH released following 800 μg LH-RH was higher than released after 100 μg LH-RH and there was a positive correlation between the total amount of LH released after LH-RH and the amount of testosterone released. It seems probable that the pre-injection level of testosterone regulates in a quantitative manner the effect of a given dose of LH-RH. In the case of successive injections of LH-RH, the plasma LH rose to a plateau but the last two treatments failed to prevent the decline in the level of LH. This suggests that testosterone, still high at the time, directly blocked the effect of LH-RH at the level of the pituitary.

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