ACTIVE IMMUNIZATION OF EWES AGAINST LUTEINIZING HORMONE RELEASING HORMONE, AND ITS EFFECTS ON OVULATION AND GONADOTROPHIN, PROLACTIN AND OVARIAN STEROID SECRETION

1978 ◽  
Vol 78 (1) ◽  
pp. 39-47 ◽  
Author(s):  
I. J. CLARKE ◽  
H. M. FRASER ◽  
A. S. McNEILLY
Keyword(s):  
Luteinizing Hormone ◽  
Plasma Levels ◽  
Follicle Stimulating Hormone ◽  
Active Immunization ◽  
Plasma Prolactin ◽  
Luteinizing Hormone Releasing Hormone ◽  
Steroid Secretion ◽  
Releasing Hormone ◽  
Highly Active ◽  
Lh Rh

Three Scottish Blackface ewes were immunized against luteinizing hormone releasing hormone (LH-RH) conjugated to bovine serum albumin (BSA) and three control ewes were immunized against BSA alone. When the antibody titre to LH-RH became raised the treated animals failed to show oestrus or ovulate; they had significantly lower levels of plasma luteinizing hormone (LH) and higher levels of prolactin than the controls, whereas the levels of follicle-stimulating hormone (FSH) were unaltered. The integrity of the hypothalamus-pituitary-gonadal system of these animals was then challenged by the injection of a highly active analogue of LH-RH and by ovariectomy. An i.v. injection of 5 μg d-serine-t-butyl6 des-glycine-NH210 LH-RH ethylamide raised plasma LH and FSH. Ovariectomy caused an eight- and ninefold rise in plasma levels of LH and FSH respectively in controls, but failed to increase plasma levels of LH and FSH in the LH-RH-immunized ewes. Plasma prolactin concentrations in the LH-RH-immunized ewes were significantly reduced by ovariectomy.

GONADOTROPHIN RELEASE BY A HIGHLY ACTIVE ANALOGUE OF LUTEINIZING HORMONE RELEASING HORMONE IN RATS IMMUNIZED AGAINST LUTEINIZING HORMONE RELEASING HORMONE

1977 ◽  
Vol 74 (2) ◽  
pp. 291-296 ◽  
Author(s):  
H. M. FRASER ◽  
J. SANDOW
Keyword(s):  
Luteinizing Hormone ◽  
Male Rats ◽  
Tertiary Butyl ◽  
Progressive Decline ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Highly Active ◽  
Normal Rat ◽  
Lh Rh

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.

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.

EFFECTS OF LUTEINIZING HORMONE RELEASING HORMONE ON PLASMA FOLLICLE-STIMULATING HORMONE AND LUTEINIZING HORMONE LEVELS IN THE FERRET

1977 ◽  
Vol 73 (1) ◽  
pp. 37-52 ◽  
Author(s):  
B. T. DONOVAN ◽  
M. B. TER HAAR
Keyword(s):  
Luteinizing Hormone ◽  
Intravenous Injection ◽  
Follicle Stimulating Hormone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Hormone Levels ◽  
Oestradiol Treatment ◽  
Gonadotrophin Secretion ◽  
Lh Rh ◽  
Lh Secretion

SUMMARY Heterologous radioimmunoassays for FSH and LH were employed to examine the effect of synthetic LH-RH upon gonadotrophin secretion in the ferret. Intravenous injection of 4 μg LH-RH induced a surge of FSH and of LH secretion in male and in female animals. In intact and in castrated males, the rise of LH was much more marked than that of FSH. The gonadotrophin response to LH-RH was greater in anoestrous than in oestrous females; FSH secretion was not enhanced during oestrus. Ovariectomized females behaved as anoestrous females with respect to LH secretion, while FSH secretion remained unchanged. Treatment of ovariectomized females with progesterone did not alter the pattern of response to LH-RH, but oestradiol treatment depressed the reaction to match that seen in oestrous females. Repetitive injections of LH-RH induced repetitive surges of FSH and LH in anoestrous females, but only of LH during oestrus: slow i.v. infusion of LH-RH induced a sustained elevation of plasma LH levels both in oestrous and in anoestrous females; again FSH levels rose only in anoestrous females. Injection of synthetic TRH did not alter gonadotrophin secretion in corresponding groups of male or female ferrets.

EFFECT OF ACTIVE IMMUNIZATION TO LUTEINIZING HORMONE RELEASING HORMONE ON SERUM AND PITUITARY GONADOTROPHINS, TESTES AND ACCESSORY SEX ORGANS IN THE MALE RAT

1974 ◽  
Vol 63 (2) ◽  
pp. 399-NP ◽  
Author(s):  
H. M. FRASER ◽  
A. GUNN ◽  
S. L. JEFFCOATE ◽  
DIANE T. HOLLAND
Keyword(s):  
Luteinizing Hormone ◽  
Active Immunization ◽  
Male Rats ◽  
Male Rat ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Accessory Sex Organs ◽  
Gonadotrophin Releasing Hormone ◽  
Low Levels ◽  
Lh Rh

SUMMARY Autoimmunity to luteinizing hormone releasing hormone (LH-RH) in adult male rats, induced by immunization with LH-RH conjugated to bovine serum albumin, resulted in atrophy of the testes and secondary sex organs and aspermatogenesis. Both immunoreactive luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum and the pituitary were reduced to low levels compared with those of control animals. It is suggested that antibodies to LH-RH can inhibit the action of endogenous hormone and that LH-RH is, in fact, the gonadotrophin-releasing hormone in the rat, required for the release of both LH and FSH.

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