Antibody production against an agonist analogue of luteinizing hormone-releasing hormone: evaluation of immunochemical and physiological consequences

1983 ◽  
Vol 103 (2) ◽  
pp. 151-157 ◽  
Author(s):  
H. M. Fraser ◽  
J. Sandow ◽  
B. Krauss
Keyword(s):  
Luteinizing Hormone ◽  
Antibody Titre ◽  
Biological Effect ◽  
Serum Testosterone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Testicular Weight ◽  
Antibody Titres ◽  
Circulating Antibodies

Abstract. Because of the widespread long-term clinical use of luteinizing hormone-releasing hormone (LRH) agonists, the possibility of antibody development to one of these, (D-Ser-(Butt)6) LRH (1–9) nonapeptide-ethylamide (buserelin), has been studied by examining sera from experimental animals and humans receiving long-term agonist-treatment for ability to bind 125I-labelled buserelin. None of the sera from monkeys, rabbits, dogs or rats receiving buserelin by sc injection or via minipump or from 81 patients receiving the agonist by sc injection or nasal spray had detectable antibodies. The immunochemistry of buserelin was investigated by actively immunizing male rabbits against the agonist. This also enabled us to determine the possibility of this stimulus to the immune response resulting in the generation of antibodies which could cross-react with endogenous LRH and neutralize its biological effect. All 41 rabbits immunized against unconjugated buserelin and all 23 immunized against buserelin conjugated to a protein carrier developed antibodies, those in the latter group producing highest titres. Serum from one of the animals immunized against unconjugated buserelin and from 9 of the animals immunized against conjugated buserelin had the capacity to bind 125I-labelled LRH. These LRH antibody titres were very low and were insufficient to cause suppression of serum testosterone concentrations or affect testicular weight except in one rabbit immunized against unconjugated agonist. The LRH antibody titre in this rabbit was always < 1:100 which our other studies have indicated to be too low to produce a biological effect. It may be that the association of low LRH antibody titre with decreased testes weight in this animal was fortuitous. We conclude that the possibility of circulating antibodies being produced to buserelin or their interfering with the action of endogenous LRH is extremely low.

Luteinizing hormone releasing hormone prevents testicular atrophy in golden hamsters exposed to a short photoperiod: temporal difference in effectiveness of administration of luteinizing hormone releasing hormone

1983 ◽  
Vol 96 (1) ◽  
pp. 147-154 ◽  
Author(s):  
H. J. Chen
Keyword(s):  
Luteinizing Hormone ◽  
Serum Testosterone ◽  
Testicular Atrophy ◽  
Temporal Difference ◽  
Luteinizing Hormone Releasing Hormone ◽  
Testosterone Concentration ◽  
Releasing Hormone ◽  
Golden Hamsters ◽  
Testicular Weight ◽  
Lh Rh

Exposure of male golden hamsters to short photoperiods of 6 h light: 18 h darkness led to testicular and accessory sex organ atrophy in 5 weeks. Short photoperiods also significantly depressed serum levels of LH, FSH, prolactin and testosterone in samples obtained by decapitation, but not in samples collected on the preceding day under ether anaesthesia. Injections of luteinizing hormone releasing hormone (LH-RH) at 09.00 h (lights on) or at 15.00 h (lights off) prevented testicular regression when compared with hamsters receiving injection vehicle only. However, the hamsters receiving LH-RH injections at lights on had significantly greater testicular weight and accessory sex organ (seminal vesicles and coagulating glands) weight and testosterone concentration than those receiving LH-RH at lights off. No increase in testicular weight was observed in hypophysectomized male hamsters given the same LH-RH injections and the same lighting regimen. These results indicate that LH-RH alone can prevent, at least partially, testicular and sex organ atrophy and increase serum testosterone concentration by stimulating release of LH and FSH in hamsters exposed to short photoperiods, involving temporal difference of LH-RH action. Further implications of the results are discussed.

Effects of luteinizing hormone releasing hormone on the gonadotrophs of hypogonadal (hpg) mice

1982 ◽  
Vol 95 (3) ◽  
pp. 331-NP ◽  
Author(s):  
I. F. W. McDowell ◽  
J. F. Morris ◽  
H. M. Charlton ◽  
G. Fink
Keyword(s):  
Luteinizing Hormone ◽  
Fold Increase ◽  
Normal Range ◽  
Cell Content ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Testicular Weight ◽  
Term Administration ◽  
Lh Rh

Hypogonadal (hpg) mice lack hypothalamic luteinizing hormone releasing hormone (LH-RH); consequently the pituitary gonadotrophs, though differentiated, remain inactive. The acute and chronic responses of gonadotrophs in hpg mice to LH-RH were studied using quantitative electron microscopy, immunocytochemistry for LH and radioimmunoassay of the gonadotrophins. Acute i.v. administration of 40 ng LH-RH to male hpg mice produced an eightfold increase in plasma LH after 5 min, but granule depletion was not detectable ultrastructurally. Vacuoles (300–600 nm) were present more frequently in gonadotrophs from hpg mice given LH-RH compared with control mice. Daily s.c. administration of 2 μg LH-RH to male hpg mice for 20 days stimulated a 63-fold increase in the pituitary content of FSH but only a twofold increase in the pituitary content of LH. Testicular weight increased fivefold but the weight of the seminal vesicles did not change. The frequency of cells immunoreactive for LH increased (× 1·6), the gonadotrophs hypertrophied (× 1·9) and the cell content of granules increased (× 2·3) to values close to the normal range. The rough endoplasmic reticulum and Golgi apparatus became more prominent. A striking result of long-term daily administration of LH-RH was the accumulation of large (1–2 μm) lipid droplets in about 40% of gonadotrophs. All these changes induced by LH-RH regressed towards the untreated hpg state when LH-RH administration was discontinued for 5 and 10 days. These results show that the gonadotrophs of hpg mice can be stimulated trophically by LH-RH, and that long-term administration stimulates the synthesis and release of the gonadotrophins but the effect on FSH is much greater than on LH.

EFFECTS OF MATING AND INJECTION OF LUTEINIZING HORMONE RELEASING HORMONE ON SERUM LUTEINIZING HORMONE AND TESTOSTERONE CONCENTRATIONS IN RABBITS

1978 ◽  
Vol 76 (3) ◽  
pp. 417-425 ◽  
Author(s):  
C. A. BLAKE ◽  
PATRICIA K. BLAKE ◽  
NANCY K. THORNEYCROFT ◽  
I. H. THORNEYCROFT
Keyword(s):  
Luteinizing Hormone ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Transient Increase ◽  
Marked Rise ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Before And After ◽  
Lh Rh

The effects of coitus and injection of luteinizing hormone releasing hormone (LH-RH) on serum concentrations of LH, testosterone and dihydrotestosterone (17β-hydroxy-5α-androstan-3-one; DHT) were tested in male rabbits. Before experimentation, male and female rabbits were housed in individual cages in the same room. Male rabbits were then bled by cardiac puncture before and after placement with female rabbits or intravenous injection of LH-RH. Serum LH, testosterone and DHT were measured by radioimmunoassay. Sexual excitement (sniffing, chasing and mounting), with or without intromission, caused a marked rise in serum testosterone and DHT concentrations in only some of the bucks. These increases were accompanied or preceded by a small, transient increase in serum LH. In the rest of the bucks, sexual excitement with or without intromission had either no effect on serum levels of all three hormones, or only serum testosterone and DHT decreased during the collection period. Similar responses were measured in bucks which were housed in a room without does for 2–4 weeks before experimentation. Injection of 10, 30 or 100 ng or 50 μg LH-RH caused serum LH, testosterone and DHT to rise in all bucks tested, but the magnitude of the rises in serum testosterone and DHT were not related to the magnitude of the LH rise. In both mated and LH-RH-injected bucks, the rises in serum testosterone and DHT were greatest in animals with low initial testosterone and DHT values. Under the conditions of this study, the data suggest that: (1) serum testosterone and DHT rise in only some male rabbits after sexual excitement (with or without intromission), (2) the rises in serum testosterone and DHT are dependent on a small transient increase in serum LH and (3) sexual excitement is less likely to cause release of LH-RH in bucks with raised serum testosterone and DHT concentrations.

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