Maintenance of Sexual Immaturity in Male Mice and Bucks by Immunization Against N-Terminal Peptides of the Follicle-Stimulating Hormone Receptor1

Abstract

The follicle-stimulating hormone is one of the two pituitary hormones that control fertility in both sexes. In the male, receptors for FSH (FSHR) are only expressed on testicular Sertoli cells. FSH plays different roles during the male life; it functions as a growth factor during development and sustains spermatogenesis in adults. However, the exact role of this hormone as an initiator of male fertility is not fully understood and few data are available concerning its involvement during the peripubertal period. We recently produced filamentous phages displaying FSHR fragments overlapping residues 18-38, which, if injected in animals, induced anti-FSH receptor immunity capable of inhibiting hormone binding. We employed this strategy to transiently inhibit FSH activity in male mice and male goats of the Saanen and the Mongolian Alpas Cashmere breeds at the prepubertal stage. Anti-FSHR peptide immunization from the age of 3 wk delayed the acquisition of fecundity in male mice by up to 1 wk. Once fertile, progeny sizes produced by mating immunized males and untreated females were found to be reduced by up to 60%. In two different breeds of goats, FSHR peptide vaccines were able to maintain circulating testosterone at low prepubertal levels for several months despite no alteration in LH levels, reflecting their ability to delay the onset of puberty. These results support the conclusion that FSH may play a central role in the male at puberty through the control of testosterone production.

Effects of long-term maternal exposure to low doses of PCB126 and PCB153 on the reproductive system and related hormones of young male goats

“…Comparable with previous studies, the onset of puberty in this study is characterized by high mean LH concentrations at about 12 -14 weeks of age that is suggested to induce testicular growth and spermatogenesis in pubescent goat kids. The relatively high concentrations of FSH are reported to enhance the production of steroid biosynthetic enzymes and increase the formation of LH receptors in the testis followed by increased production of testosterone (Foster 1994, Hall 1994, Ahmad et al 1996, Brooks et al 1996, Foster et al 2002, Abdennebi et al 2003. In conformity with the female kids in our parallel study (Lyche et al 2004a), the PCB153-exposed male kids showed a significant effect of treatment on the mean plasma LH concentration.…”

Enhanced Suppression of Fertility Can be Achieved by Priming with FSHR and Eppin and Further Boosting with Their B‐cell Epitope Peptides

“…Thus, there is an urgent need for a better contraceptive method that is acceptable, effec-tive, reversible and available both in the developed and in the developing nations. 8,9 With respect to gamete-associated components, research has focused on the relationship between sperm antigens and fertility in past decades. Mammalian reproduction begins with the production of male and female gametes followed by their unification within a fertilized egg.…”

“…6,7 The ECD of FSH receptor (FSHR) has also been considered a suitable target for a male vaccine, as it is expressed exclusively on testicular Sertoli cells. 8,9 With respect to gamete-associated components, research has focused on the relationship between sperm antigens and fertility in past decades. Among numerous molecular candidates related to sperm, epididymis protease inhibitor (Eppin) is a promising candidate.…”

Expression and purification of the extracellular domain of the human follicle‐stimulating hormone receptor using Escherichia coli

“…The distribution pattern of FSHR permits its use in tumor‐targeting therapy strategies . Additionally, the ECD of FSHR has been used as an immunogen to produce a contraceptive vaccine . However, the recognition and specific binding of FSH to its receptor have not yet been elucidated.…”