Nonmammalian vertebrate models in studies of brain-steroid interactions

Abstract

Estrogen formation in brain and pituitary mediates certain androgen actions in central targets. Goldfish (Carassius auratus) and quail (Coturnix coturnix japonica) have been advantageous for studying the role of locally formed estrogen in autoregulating aromatization and in controlling estrogen receptor occupancy, androgen receptor levels, and behavioral expression. Data from these two experimental models reveal a molecular basis for androgen-estrogen synergism in neuroendocrine tissues and for alterations in androgen sensitivity/responsiveness. These mechanisms are essential components of seasonal reproduction in the test species and may have wider relevance for cyclicity in other vertebrates, including mammals. BRAIN AROMATASE: AN OVERVIEWFollowing development of high specific activity radiolabeled steroids in the late '~O S , pathways of steroidogenesis in glandular tissues were intensively investigated (for review, Engel, '75). During this era it was established that androstenedione and testosterone (T) are the immediate and obligatory precursors of estrone and estradiol (E2), respectively. The enzyme catalyzing this reaction was termed aromatase, a name describing transformation of the A4, 3-ketone-A ring of androgens to the aromatic benzene ring of natural estrogens. Although initial studies focused primarily on human placenta and human or porcine ovary, tissues exceptionally rich in aromatase, it was soon determined that estrogen is synthesized in testis, adrenal, and a variety of non-glandular tissues such as fat and muscle (Longcope et al., '78). Owing to their large mass, peripheral sites of estrogen synthesis make a substantial contribution to the circulating estrogen pool when androgen substrates are available in the peripheral blood.In 1971, the first identification of aromatase was made in human fetal brain and shortly thereafter in rat, rabbit, and mouse brain (Naftolin et al., '75). Significantly, enzyme activity was restricted to regions with E2-target cells and known to control reproduction and sex behavior (hypothalamus = HTH, preoptic area = POA, amygdala).These findings led to proposal of the "aromatization hypothesis": namely, that aromatization of 0 1990 WILEY-LISS, INC.circulating androgen in the brain itself is required for the full expression of androgen actions in central targets. Although this hypothesis explained the well-known "paradoxical effects" of sex steroids on vertebrate behaviors (Young, ,611, it met with some skepticism at first, due in part to extremely low levels of estrogen actually formed in brain. Proof that even small quantities of active hormone may be physiologically important when synthesized in close proximity to sites of action was obtained by experiments showing that peripheral administration of [3H]T to gonadectomized-adrenalectomized rats resulted in nuclear-bound [3HlE2 in brain regions with aromatase activity but not in other areas (Lieberburg and McEwen, '77). It is noteworthy here that unmetabolized T and 5a-dihydrotestosterone (DHT), another T m...

Internal and external factors controlling reproduction in the African catfish,Clarias gariepinus

“…According to Callard et al (1990), androgens could exert an effect on GTH secretion via androgen receptors (AR) or estrogen receptors (ER) in the brain, as aromatase, AR and ER were demonstrated in the diencephalic pre-optic area. Furthermore, the aromatase activity showed a strong correlation with reproductive activity.…”

Endocrine control of sexual behavior in sneaker males of the peacock blenny Salaria pavo: Effects of castration, aromatase inhibition, testosterone and estradiol

“…Thus, for some fish species, T aromatization into E2 may also mediate the expression of male sexual displays. The largely ignored role of brain aromatization of androgens on fish sexual behavior is also surprising as teleosts present by far the highest levels of brain aromatase activity in vertebrates (Callard et al, 1990) and, in fish, aromatase occurs in brain areas involved in the control of reproductive behavior (Forlano et al, 2001;Menuet et al, 2003Menuet et al, , 2005 and peaks during the species reproductive seasons (e.g. Gelinas et al, 1998;Piferrer, 2002, 2003;Forlano and Bass, 2005).…”

Actions of sex steroids on kisspeptin expression and other reproduction-related genes in the brain of the teleost fish european sea bass

“…Additionally, this work has provided evidence that the Kiss2/Gnrh-1 system modulates the activity of gonadotrophs involving the neuroendocrine areas of the forebrain-midbrain . As testosterone is an aromatizable androgen, and fish present the highest levels of brain aromatase activity in vertebrates (Callard et al, 1990;Diotel et al, 2010), changes in cyp19b expression levels were analysed. The high cyp19b mRNA levels in the brain of male sea bass parallel reduced ar mRNA expression in the hypothalamus and increased transcriptional activity of hypothalamic erβ1 and pituitary erα in GDX+T.…”