Contraception as prevention and therapy: sex steroids and the brain.
The brain is one of the specific target tissues for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in brain areas of the central nervous system (CNS), through the binding with specific receptors. Specific receptors for gonadal steroids have been identified in the amygdala, hippocampus, basal forebrain cortex, cerebellum, locus ceruleus, midbrain rafe nuclei, glial cells, pituitary gland, hypothalamus and central gray matter. At the hypothalamic level, the principal target for sex steroids is those neurons producing the pulsatile release of the gonadotropin releasing hormone (GnRH), localized in the mediobasal hypothalamus and the arcuate nucleus. The GnRH release depends on the complex and co-ordinated interrelationships among gonadal steroids, pituitary gonadotropins and neuroactive transmitters, such as the noradrenaline, dopamine, opioid peptides (beta-endorphin), acetylcholine, serotonin, gamma-aminobutyrric acid, corticotropin releasing hormone and neuropeptide Y. The interplay of these control mechanisms is governed by peripheral feedback signals; as well as the input from higher brain centers they may modify the GnRH secretion. The anterior pituitary lobe is the best known target tissue for endogenous or exogenous sex steroid hormones, because it is possible to detect luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in blood, as the expression of the pituitary cells' activity. The synthesis and release of FSH and LH by the gonadotropic cells depend upon the peripheral control of gonadal hormones and the GnRH hypothalamic release. In summary, during a woman's reproductive life, the interaction between neurotransmitters, neuropeptides and gonadal hormones modulates the hypothalamo-pituitary-gonadal axis by acting selectively on the synthesis and release of GnRH and of pituitary gonadotropic hormones. The increased use of oral contraceptives in the last 30 years and, in general, of sex steroid hormone derivative therapies, has led to the study of the biochemical and metabolic properties of the different progestin molecules available in hormonal therapies by focusing attention on the interactions between estrogens and progestins in the modulation of the hypothalamo-pituitary-gonadal axis. The different kinds of estrogen and progestin molecules used in oral contraceptives inhibit the ovulatory process and may interfere with other sex steroid hormone receptors, thus exerting multiple effects in each target tissue.
Stomati
M
M
Department of Obstetrics and Gynecology, University of Pisa, Italy.
Genazzani
A D
AD
Petraglia
F
F
Genazzani
A R
AR
D000728:Androgens / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology*; D003276:Contraceptives, Oral / Q000494:pharmacology*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007986:Luteinizing Hormone / Q000502:physiology; D011372:Progestins / Q000502:physiology*
D000728:Androgens; D003276:Contraceptives, Oral; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011372:Progestins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone