Effects of long-term immunization against LHRH and androgen treatment on gonadal function

Ladd, A; Tsong, Yun-Yen; Prabhu, Girish; Thau, Rosemarie B.

doi:10.1016/0165-0378(89)90029-6

Cited by 30 publications

(17 citation statements)

References 21 publications

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“…From the immunological perspective, it would seem that LHRH, the master hormone responsible for overall regulation of hypothalamus-pituitary-gonadal interactions, is especially well protected from interference: the low molecular weight of this highly conserved "self' protein [1,5,15], its pulsatile release into the blood stream, and its short halflife [16,17] serve to render this molecule "... incapable of inducing production of antibodies that result from the repeated use" [18]. It has been reported previously that it is indeed possible to induce biologically effective antibodies against LHRH in small laboratory animals such as rats and rabbits [10][11][12] and in larger animals such as sheep, pigs, and monkeys [6]. The studies reported here suggest that rapid antibody responses to LHRH may also be induced in genetically more diverse animals such as dogs and cats through the use of pharmaceutically acceptable immunogenic materials only.…”

Section: Discussionmentioning

confidence: 98%

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Development of an Antifertility Vaccine for Pets Based on Active Immunization against Luteinizing Hormone-Releasing Hormone1

Ladd¹,

Tsong²,

Walfield³

et al. 1994

Biology of Reproduction

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Male dogs and cats were immunized against LHRH in order to evaluate the feasibility of an immunological approach to pet contraception. In the first study, dogs were immunized with 100, 500, or 2500 micrograms of LHRH conjugated to tetanus toxoid. A significant decline in serum testosterone (T) levels was observed in all immunized dogs, reaching castration levels in some animals by Week 4 and remaining suppressed in all the immunized dogs through the course of the study. Testicular histology suggested arrest of spermatogenesis (infertility). The effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed by "immunological castration" was restored as antibody titers declined. Effective antibodies were rapidly reinduced in dogs by a single injection of LHRH1-TT. In contrast, the level of antibodies induced in male cats (study 3) was not sufficient for "immunological castration." The conclusion was that active immunization against LHRH could provide a cost-effective, nonsurgical, reversible means to control the fertility of companion animals.

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Section: Discussionmentioning

confidence: 98%

“…Anti-LHRH titers were measured by a previously described RIA [10][11][12]. Nonspecific binding was determined by measuring antibody titers in nonimmunized animals and did not exceed 4% binding or 0.3 nmol/L.…”

Section: Rasmentioning

confidence: 99%

Development of an Antifertility Vaccine for Pets Based on Active Immunization against Luteinizing Hormone-Releasing Hormone1

Ladd¹,

Tsong²,

Walfield³

et al. 1994

Biology of Reproduction

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“…It is possible to inhibit sperm production indirectly by suppressing the secretion of testosterone (T), which is required for spermatogenesis. This has been achieved variously by using exogenous androgens [1][2][3][4][5] to inhibit the release of LH, and by blocking the action of GnRH [6][7][8][9][10][11][12]. However, drugs such as gossypol [13][14][15], tolnidamine [16], and sulfasalazine [17][18][19][20][21] can also directly inhibit spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Maintenance of Sexual Function with Testosterone in the Gonadotropin-Releasing Hormone-Immunized Hypogonadotropic Infertile Male Rat

Awoniyi¹,

Reece²,

Hurst³

et al. 1993

Biology of Reproduction

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We have previously shown that active immunization against GnRH in the mature male rat can predictably produce hypogonadotropic hypogonadism and azoospermia and, further, that normospermia and normal fertility can be restored by testosterone (T) administration alone. The objective of this study was to explore the hypothesis that GnRH-immunized azoospermic rats could be supplemented with T doses sufficient to restore sexual behavior, but insufficient to support adequate spermatogenesis or to allow restoration of fertility. Adult male rats of proven fertility were immunized against GnRH and supplemented with 2-, 4-, or 8-cm T implants or with empty implants. Eight weeks later, fertility was evaluated; concentrations of serum T, LH, FSH, growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) were determined; sperm number was obtained from the testis; and weights of androgen-dependent organs were measured. GnRH immunization and T supplementation resulted in restoration of organ weights and of fertility in a dose-dependent manner. GnRH immunization with or without T supplementation resulted in the absence of circulating gonadotropins, but had no effect on serum GH, PRL, or TSH levels. Whereas all control animals were fertile, rats that received either empty or 2-cm T implants were completely infertile. Rats that received 4-cm or 8-cm T implants were fertile in 60% and 100% of cases, respectively. Sexual behavior of rats with empty and with 2-cm T implants was compared at 10-18 wk after immunization with GnRH. GnRH-immunized rats given empty implants displayed negligible sexual activity, but those with 2-cm T implants displayed sexual activity equivalent to that of untreated controls despite complete infertility.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The rationale for these vaccines is to induce the formation of antibodies and/or cell-mediated immunity to intercept selectively a process critical to the success of reproduction. A number of potential antigens are being investigated (1)(2)(3)(4)(5)(6)(7). Among these are hormones, which play an important role in the regulation of fertility.…”

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confidence: 99%

A vaccine that prevents pregnancy in women.

Talwar

Singh

Pal

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

198

134

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We report here results of clinical trials on a birth control vaccine, consisting of a heterospecies dimer of the .3 subunit of human chorionic gonadotropin (hCG) associated noncovalently with the a subunit of ovine luteinizing hormone and coijugated to tetanus and diphtheria toxoids as carriers, that induces antibodies of high avidity (Ka 1010 M-) against hCG. Fertile women exposed to conception over 1224 cycles recorded only one pregnancy at antibody titers of >50 ng/ml (hCG bioneutralization capacity). The antibody response declines with time; fertility was regained when titers fell to <35 ng/ml. This study presents evidence of the feasibility of a vaccine for control of human fertility.A number of contraceptive methods are available; they do not, however, suit all potential users. There is need to develop additional methods, in particular those that are reversible, require only periodic intake, and do not disturb menstrual regularity or bleeding. Vaccines regulating fertility offer promising prospects to meet these specifications. The rationale for these vaccines is to induce the formation of antibodies and/or cell-mediated immunity to intercept selectively a process critical to the success of reproduction. A number of potential antigens are being investigated (1-7). Among these are hormones, which play an important role in the regulation of fertility. Human chorionic gonadotropin (hCG) is an early signal of conception and is considered essential for establishment and maintenance of early pregnancy. An advantage in choosing hCG as a target for immunocontraception is that its inactivation would not interfere with other physiological processes in the female, such as ovulation and production of sex steroid hormones.Carrier conjugation with tetanus toxoid (TT) was proposed as a strategy to overcome the immunological tolerance of a woman against hCG (8). This initial prototype vaccine (/3hCG-TT adsorbed on alum) had limitations. It induced high antibody titers in only a small percentage of women, and those with low titers were not protected from pregnancy (9). Three changes were made to enhance immunogenicity.(i) An adjuvant, the sodium phthalyl derivative of lipopolysaccharide, was included in the first injection. This nonpyrogenic adjuvant is usable in aqueous phase (10). Its use doubled, on average, anti-hCG titers and increased the frequency of high responders.(ii) The intrinsic immunogenicity of (3hCG was enhanced by associating it noncovalently with the a subunit of ovine luteinizing hormone (LH) to form a heterospecies dimer (HSD), a laboratory-made hormone that attains a conformation which recognizes receptors on target tissues (whereas isolated subunits do not) and generates a steroidogenic response even superior to that by hCG (11). HSD linked to carriers was indeed found to be more immunogenic than ,8hCG in rats and monkeys (12). Moreover, the antibodies had better capacity to neutralize the bioactivity of hCG (11,13 It was important to determine whether the antibodies induced by the HSD-and 8hC...

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Effects of long-term immunization against LHRH and androgen treatment on gonadal function

Cited by 30 publications

References 21 publications

Development of an Antifertility Vaccine for Pets Based on Active Immunization against Luteinizing Hormone-Releasing Hormone1

Development of an Antifertility Vaccine for Pets Based on Active Immunization against Luteinizing Hormone-Releasing Hormone1

Maintenance of Sexual Function with Testosterone in the Gonadotropin-Releasing Hormone-Immunized Hypogonadotropic Infertile Male Rat

A vaccine that prevents pregnancy in women.

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