title: Dimorphic expression of testosterone metabolizing enzymes in the hypothalamic area of developing rats.
abstract: Androgen transformation into estrogens through the aromatase enzyme, occurring in the rat hypothalamus during fetal life, leads to male-specific sexual differentiation of brain. Aromatase shows a peak of expression and activity in a limited period during late gestation; however, the possible dimorphism in its expression during embryogenesis is unclear. One of the mechanisms controlling tissue-specific aromatase expression might be the formation of transcript variants, that differ in the 5'-untranslated regions (5'-UTR). Exon If is the major 5'-UTR used in rodent hypothalamic-preoptic area, with low amounts of other variants encoded by different exons I also present. Another enzymatic conversion, possibly involved in brain differentiation, is the 5 alpha-reduction of Testosterone to DHT, catalyzed by two 5 alpha-reductases (5 alpha-R type1 and 2). Aim of the present study is to evaluate, in parallel, by semiquantitative RT-PCR, the dimorphic profile of the three enzymes and the pattern of the brain-specific aromatase expression in male and female rats from gestation-day 16 to postnatal-day 5 (or 15 only for 5 alpha-R1). It has been observed that, in both sexes, 5 alpha-R1 is significantly higher around birth than prenatally, and that 5 alpha-R2 expression appears to be higher in males than in females, particularly just after birth. Moreover, aromatase has two expression peaks, that are male-specific, before and after birth; only exon If is used in males, while different transcripts might be present in females postnatally. It is concluded that rodent brain sexual differentiation probably involves the activation of both 5 alpha-R2 and aromatase enzymes in a sex- and time-specific pattern.
authors.affiliation: Department of Endocrinology, University of Milan, Via G. Balzaretti, 9, 20133, Milano, Italy. fabio.celotti@unimi.it
authors.forename: A
authors.initials: A
authors.lastname: Colciago
authors.forename: F
authors.initials: F
authors.lastname: Celotti
authors.forename: A
authors.initials: A
authors.lastname: Pravettoni
authors.forename: O
authors.initials: O
authors.lastname: Mornati
authors.forename: L
authors.initials: L
authors.lastname: Martini
authors.forename: P
authors.initials: P
authors.lastname: Negri-Cesi
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015139:Blotting, Southern; D005091:Exons / Q000235:genetics; D005260:Female; D007031:Hypothalamus / Q000201:enzymology* / Q000254:growth & development*; D008297:Male; D009841:Oligonucleotides / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013739:Testosterone / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; D012333:RNA, Messenger; D013739:Testosterone; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase