Active Immunization Against Gonadotropin‐Releasing Hormone Combined With Androgen Supplementation Is a Promising Antifertility Vaccine for Males

Ladd, A; Prabhu, Girish; Tsong, Yun-Yen; Probst, T; Chung, Wonil; Thau, Rosemarie B.

doi:10.1111/j.1600-0897.1988.tb00215.x

Cited by 30 publications

(16 citation statements)

References 16 publications

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“…2 levels of antibodies against LHRH leads to the suppression of reproductive behavior in both males and females, the suppression of synthesis and secretion of gonadotropins and gonadal steroid hormones, gonadal atrophy, and arrest of gametogenesis [6]. These observations suggested the potential application of immunization against LHRH for the regulation of gonadal functions and fertility in domestic animals [7,8] and humans [9,10]. The studies reported here were conducted in male dogs and cats.…”

Section: Introductionmentioning

confidence: 87%

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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: Introductionmentioning

confidence: 87%

“…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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“…Thus, vaccines utilising GnRH would suppress both sperm and testosterone production in males. This complicates their use as contraceptive vaccines because androgen supplementation is necessary to maintain secondary sex characteristics and libido [34]. Although GnRH-based vaccines have been produced for use as contraceptives in animals [35], their development so far for use in humans has been aimed primarily at treating sex hormone-dependent diseases including cancer [24,36].…”

Section: Gonadotropin-releasing Hormone (Gnrh)mentioning

confidence: 99%

“…The phase II trials were carried out in India, with informed written consent obtained from healthy females aged [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Three primary injections were given at 6 week intervals, and boosters administered when necessary to maintain antibody titres above 50ng/ml of hCG bioneutralising specific antibody.…”

Section: Human Chorionic Gonadotropin (Hcg)mentioning

confidence: 99%

The development of contraceptive vaccines

Delves

2002

Expert Opinion on Investigational Drugs

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The use of vaccination as a means of controlling fertility was established during the last decade with the publication of a successful Phase II trial demonstrating the efficacy of this approach to family planning. However, only this one Phase II trial has been completed despite a plethora of hormonal and gamete antigens that have been proposed as candidate vaccines. Improvements in the design and formulation of contraceptive vaccines are underway and will be a necessary prelude to further clinical trials. AbstractThe use of vaccination as a means of controlling fertility was established during the last decade with the publication of a successful phase II trial demonstrating the efficacy of this approach to family planning. However, only this one phase II trial has been completed despite a plethora of hormonal and gamete antigens that have been proposed as candidate vaccines. Improvements in the design and formulation of contraceptive vaccines are underway and will be a necessary prelude to further clinical trials.

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Active Immunization Against Gonadotropin‐Releasing Hormone Combined With Androgen Supplementation Is a Promising Antifertility Vaccine for Males

Cited by 30 publications

References 16 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

The development of contraceptive vaccines

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