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The paediatric endocrinologist is frequently asked whether pubertal development in a girl is normal, early or too early (precocious). This review will cover all clinical expression of premature development of puberty: central precocious puberty (neurogenic, secondary, and idiopathic) where treatment with GnRHa is considered, early puberty, partial puberty or pubertal variants and peripheral or pseudo precocious puberty related to an antonomous hypersecretion of estrogens by the ovaries. A special attention should be paid also to the role of environmental disruptors in the development of peripheral precocious puberty. GnRHa treatment should be considered only when evidence of central activation of the gonadotropic axis is proved by the LHRH-test.

Androgens play a crucial role in the development, maintenance and regulation of male phenotype and reproductive physiology through the androgen receptor, a transcription factor. Testosterone or dihydrotestosterone binding induces a trans-conformation of the androgen receptor and allows its translocation into the nucleus, where it recognizes specific DNA sequences. Recent developments in molecular genetics, as well as structural analysis of the androgen receptor, allow a better understanding of the structure/function relationship of this nuclear receptor. Molecular analyses of androgen insensitivity syndrome, as well as hormone-resistant prostate cancer, Kennedy's disease and isolated male infertility, have been proved useful as privileged models for this purpose. In the absence of identified AR receptor mutations in androgen insensitivity syndromes, abnormalities of transcriptional cofactor should be considered. Finally, identification of androgen-dependent genes will be helpful for evaluating the degree of the molecular defect of androgen action within target cells.

In order to improve the non aggressive diagnosis of hepatic metastasis from digestive neoplasm, the authors analyzed the following biological parameters: aminotransferases, alkaline phosphatase and lacticodehydrogenase isoenzymes, gammaglutamyl-transpeptidase, conjugated and total bilirubin, C-reactive protein, type A, G, M immunoglobulins, C3 complement factor, alpha-1 acidic glycoprotein (orosomucoid), haptoglobin, ceruloplasmin, transferrin, albumin, prealbumin, ferritin. This work included 54 patients with digestive tract cancer (esophageal, gastric, colic, rectal, anal localizations), divided in two groups: M- (n = 27), without hepatic metastasis), and M+ (n = 27, with histological confirmed hepatic metastasis). The Mann-Whitney test showed significant differences for 12 parameters between the 2 groups. With more than 60% sensitivity (Se) and specificity (Sp), according to the ROC curves, the following parameters can be selected: Total alkaline phosphatase (Se 89%, Sp 70%) and their macromolecular H2 fraction, lacticodehydrogenase fraction 4 (Se 63%, Sp 63%), gammaglutamyl-transpeptidase (Se 85%, Sp 82%), ceruloplasmin (Se 64%, Sp 65%), aspartate-aminotransferase determination (Se 63%, Sp 65%).

The human prostate is a complex organ composed of four glandular zones that differ in their histology and biology. In addition to this anatomical organization, the prostate is mainly composed of epithelial and mesenchymal tissues. Two pathologies affect the growth of the prostate: cancer and benign prostatic hyperplasia. Anatomical and pathological studies have shown that stromal enlargement is the first step in the process of BPH and that both transition and periurethral regions are the exclusive sites of origin. Because the first step of androgen action is the reduction of testosterone into dihydrotestosterone by the 5 alpha-reductase, it have been postulated that modification of this enzymatic activity may play an important role in BPH development. However DHT production alone cannot explain the hyperplastic development of the gland. Thus it has also been postulated that androgen-growth factor interaction may be an important feature of this growth: these growth factors include the IGF axis. An interaction between androgen pathway and sympathethic system, via alpha-adrenoreceptor may also be suspected.

The various processes involved in sexual differentiation have been considerably clarified over the last few years through advances in biochemistry and molecular genetics. The cloning of the gene responsible for testicular determination SRY, of the anti-Müllerian hormone and anti-Müllerian hormone receptor genes, of the several steroidogenic enzymes genes, of the 5 alpha-reductase type 2 gene and of the androgen receptor gene has permitted to elucidate the molecular defects causing abnormal sexual differentiation. These data have brought a substantial impact on the understanding of human male sexual differentiation and its main disorders.

Turner syndrome is a complex human phenotype most commonly seen in association with a 45,X karyotype and it has been proposed that the phenotype is the result of monosomy for genes common to the X and Y chromosomes. Detection of unrecognized Y derived material is now possible by PCR of the SRY gene. Its presence is correlated with the presence of testicular tissue, known to increase the risk of developing gonadal neoplasia. Study of Y chromosome allowed the localisation of a candidate gene for the development of gonadoblastoma, GBY. Moreover, some groups described genes on the Y chromosome whose defects seem to be involved in the development of Turner stigmata: ZFY and RPS4Y. In conclusion; molecular genetics of the Y chromosome develops new pathophysiological and fundamental perspectives of the molecular genetics of the Turner syndrome.

In a large kindred with Reifenstein syndrome, we performed the molecular analysis of the androgen receptor gene. Since the biochemical characteristics of the androgen receptor, determined on the cultured genital skin fibroblasts, showed a drastic decrease of the androgen binding capacity, we assumed that a point mutation was located in exons 4-8 encoding the carboxy-terminal domain of the receptor. Enzymatic amplifications of these exons did not point out any deletions. Direct sequencing showed a G-A point mutation at position 2818 of exon 7 responsible for an arginine-histidine substitution at position 840 of the androgen receptor. The presence of the same mutation has been reported by other groups in four unrelated patients. Its association with different phenotypes of androgen insensitivity and different biochemical characteristics of the androgen receptor pointed out the complexity of the genotype-phenotype relationship in androgen insensitivity. Moreover the identification of the point mutation gave us the opportunity to perform a prenatal exclusion diagnosis of Reifenstein syndrome in this high-risk family.

Androgen insensitivity syndromes are X-linked disorders. Restriction fragment length polymorphism analysis of the androgen receptor gene showed that deletions were infrequent. Some mutations have been described. In these conditions, in high-risk family, carrier diagnosis is impossible unless identification of mutations is made. It is thus necessary to detect androgen receptor gene polymorphism in order to differentiate the two maternal X chromosomes. Two androgen receptor gene polymorphisms have been reported (Hind III and exon 1). In this study we analyzed these two gene polymorphisms to detect carriers in at-risk families. The combined results of the two analyses allowed us to detect carriers in 45% of the studied families. In two families the prenatal diagnosis of androgen insensitivity syndrome was performed.