Acta endocrinologica. Supplementum最新文献

1. Monitoring of gonadotropin therapy is essential to reduce the risk of hyperstimulation and multiple pregnancies. Biochemical methods for the measurement of estrogen production should be done in conjunction with ultrasonic scanning of the growing follicles. 2. The joint action of clomiphene and gonadotropins has not been adopted for routine gonadotropin therapy but is useful for inducing multiple ovulations in women undergoing in vitro fertilization. 3. Pulsatile administration of gonadotropins has not been shown to avoid multiple follicular development and therefore has no advantage over routine methods of administration. 4. Gonadotropin preparations with a high ratio of FSH to LH would theoretically be more suitable for the treatment of polycystic ovarian disease than the usual preparations with a 1:1 ratio on account of the high basal LH levels in these patients. In experiments so far the results obtained have been no better however.

The application of RIAs for the gonadotropins to the study of domestic animal reproduction has depended on the availability of sensitive and specific reagents, automated systems for increased throughput and an awareness of the assay errors. Illustrations are given on the measurement of seasonal, surge and episodic changes in LH secretion and the advantages gained by such investigation are outlined.

The four human glycoprotein hormones FSH, LH, CG and TSH are closely related in structure, each consisting of a common alpha-subunit and a specific beta-subunit. Amino acid sequences have been established by standard methods of protein sequencing and confirmed by base sequencing of the cDNAs encoding for the polypeptide units. Speculation on the structures involved in the binding of subunits and binding to receptors has been based on examination of these sequences for common or similar regions. There are asparagine-linked carbohydrate chains attached to the subunits and in addition O-glycosidically linked carbohydrate chains in beta-CG attached to serine molecules. The carbohydrates are essential for full biological activity. The progress so far and future possibilities for the synthesis of these glycoprotein hormones by the technique of genetic engineering are discussed.

A review is presented of tests used to diagnose either isosexual precocity or delayed pubertal development in children. The importance of auxological measurements is emphasised. Attention is drawn to the limitations of measuring basal or stimulated levels of LH, FSH and the sex steroids for the diagnosis of these conditions. The value of gonadotropin profiles is discussed for either diagnosis or for assessing the response to GnRH therapy in patients with either isosexual precocity or isolated gonadotropin deficiency. Examples are given of new therapeutic agents and procedures that are used to treat these two groups of patients. These include GnRH agonists for treatment of children with isosexual precocity either alone, or in combination with inhibitors of aromatase or C17-20 lyase enzyme activity in the biosynthesis of the sex steroids and pulsatile GnRH for the treatment of adolescents with gonadotropin deficiency.

The secretion of FSH appears to be dominated by factors controlling the inhibition of synthesis and release acting directly at the level of the gonadotrope in the pituitary. Only minimal amounts of GnRH are necessary to stimulate and maintain the secretion of FSH, and, in contrast to LH, the release of FSH is closely linked to the rate of synthesis. Estradiol is a potent inhibitor of FSH release acting directly at the gonadotrope to inhibit mRNA transcription. In vivo, estradiol alone in physiological concentrations cannot maintain plasma concentrations within the normal levels seen during the estrus or menstrual cycle. It is probable that estradiol acts synergistically with inhibin both of which are secreted by the developing follicle. Inhibin secretion in the follicle is dependent on FSH. During the follicular phase in sheep and women peripheral plasma concentrations of inhibin remain unchanged or decline in parallel with those of FSH, and inversely to estradiol. In the luteal phase, the human corpus luteum secretes inhibin under the influence of LH. Thus inhibin together with both estradiol and progesterone secreted by the corpus luteum, accounts for the suppression of FSH and thus follicular development in the luteal phase of the human menstrual cycle.

GnRH analogues suppress LH fluctuations and produce a condition of hypogonadotropic hypogonadism. This action combined with treatment with human menopausal gonadotropins (hMG) has been exploited in programmes of induction of follicular growth in infertile women for both in vivo and in vitro fertilisation. There is improved clinical control over the process of ovulation and the phenomenon of premature luteinization in women with polycystic ovary disease has been eliminated.

Techniques are described for the extraction and purification of FSH and LH from human pituitary glands. The methodology uses acetone and alcohol for dehydration, extraction and precipitation of materials from both acetone preserved and fresh frozen glands. The processing involves the use of anion and cation exchange chromatography, adsorption techniques, and molecular sieve chromatography. Immunoaffinity extraction and purification of the gonadotropic hormones are also described. The specific activities of the LH preparations from acetone-preserved glands and from fresh frozen glands ranged from 11,200 to 12,640 IU/mg (68/40) and contained less than 0.2% TSH and FSH contamination. The yield varied from 9% to 18%. The specific activities of the FSH preparations from fresh frozen glands and from acetone preserved glands by affinity extraction (4990 and 4600 IU/mg 78/549) were higher than that from acetone preserved glands (3235 IU/mg). The LH and TSH contamination was less than 0.5%. The highest yield of FSH (34%) was obtained by affinity extraction. The preparations are of sufficient purity for use as immunogens and standards and for the preparation of radioligands to be used in specific and sensitive immunoassays.