Abstract

PIP: The theoretical background for development of steroid contraceptive agents, LH-RH agonists and antagonists, heterocyclic abortifacients, male contraceptive agents, and contraceptive vaccines are reviewed, with emphasis on basic steroid receptor research. Recent findings confirming the steroid receptor interaction theory proposed in 1960 are described. This model suggests that the steroid enters target cells by diffusion and binds to specific protein receptors in the cytoplasm. The steroid- receptor complex moves to the nucleus by concentration gradient and binds to chromatin or DNA, altering gene expression. both estrogen and progesterone receptors are asymmetric peptides with rigid hydrophobic domains that bind specific steroids, doisynolic acids, stilbenes, gem- diarylethylenes, triarylpropiones, all of which have a set distance between a phenolic hydroxyl and another hydroxyl analogous to the steroid C17-beta-hydroxyl groups. Antiprogestins without glucocorticoid activity are being sought. LH-RH antagonists are being developed by substituting amino acids in the peptide. A large variety of heterocyclic compounds, 26 types, with abortifacient activity, acting by interfering with blastocyst binding to the deciduum is described, such as a series of quinine derivatives. Male antifertility agents must block spermatogenesis without affecting libido or sperm maturation. Combined steroid pills with cyproterone acetate and an androgen are in clinical trials. The most hopeful immunologic contraceptives are vaccines based on part of the beta subunit of hCG, sperm antigens and zona pellucida antigens.