Rationale

An immunological approach to reproductive physiology, asking fundamental questions, is paying off at the basic, strategic, and applied levels. Perturbation of the closely interrelated feedback systems, shown in Figure 1 and Table 1, is giving us a better understanding of the efficacy, specificity, and practicality of intervention, together with the priorities, benefits, and risks of the sites now available. In theory, active or passive neutralization has many advantages, as a

Hypothalamus

Pituitary

Ovary Follicle

Corpus luteum

Uterus Embryo

Hypothalamus

Ovary Follicle

Corpus luteum

Figure 1 Reproductive endocrine feedback in primates. GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; P„, progesterone; E2, estradiol 17-0; E,, estrone; T4, testosterone; In, inhibin; A, androstene-dlone; ABP, androgen-binding protein

Table 1 Neutralization effects with antibodies

Hormone neutralized

Female Hypothalamus Pituitary Ovary

Ovum Embryo

Male Sperm

GnRH LH/FSH

Progesterone/estradiol 17-p

Estradiol

Inhibin

Estrone/androstenedione Zona pellucida Platelet activating factor] Early pregnancy factor J Chorionic gonadotropin

LDH-CD4 isoenzyme Sperm surface antigens

Effect

Reproductive shutdown

Prevents ovulation, disrupts feedback

Broad effects on LH increase

FSH increase and behavior

FSH increase

Raises ovulation rate

Blocks fertilization

Inhibit fertility; unconfirmed

Prevents implantation

Reduces fertility Reduce fertility controlled response can be short or long term, potentially reversible, relatively noninvasive, and well targeted either to a system or to a specific site. In practice, caveats remain concerning species specificity, induced autoimmunity or its consequences when continually secreted antigens are inhibited, or unpredictable side-effects through the neutralization of as yet poorly understood genes, proteins, enzymes or steroids that may have multiple roles or feedback links.

Consequently, neutralization with antibodies may be utilized to: 1) advance understanding of the mechanisms of action of factors affecting reproductive processes; 2) suppress fertility in the management of human and animal reproduction; 3) enhance fertility in certain cases; 4) understand the etiology of disorders such as precocious puberty, polycystic ovarian disease and premature menopause; or 5) develop generic methodologies such as those of radioimmunoassay, ELISA and other immunoassays that have transformed the field.

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