ENDOCRINE REGULATION OF GONADOTROPIN AND GROWTH-HORMONE GENE-TRANSCRIPTION IN FISH

The pituitary of a number of teleosts contains two gonadotropins (GtHs ) which are produced in distinct populations of cells; the beta subuni t of the GtH I being found in close proximity to the somatotrophs, whi le the II beta cells are more peripheral. In several species the GtH b eta subunits are expressed at varying levels throughout the reproducti ve cycle, the I beta dominating in early maturing fish, after which th e II beta becomes predominant. This suggests differential control of t he beta subunit synthesis which may be regulated by both hypothalamic hormones and gonadal steroids. At ovulation and spawning, changes also occur in the somatotrophs, which become markedly more active, while p lasma growth hormone (GH) levels increase. In a number of species, GnR H elevates either the I beta or the II beta mRNA levels, depending on the reproductive state of the fish. In tilapia, the GnRH effect on the II beta appears to be mediated through both cAMP-PKA and PKC pathways . GnRH also stimulates GH release in both goldfish and tilapia, but it increases the GH transcript levels only in goldfish; both GnRH and di rect activation of PKC are ineffective in altering GH mRNA in tilapia pituitary cells. Dopamine (DA) does not alter II beta transcript level s in cultured tilapia pituitary cells, but increases GH mRNA levels in both rainbow trout and tilapia, in a PKA-dependent manner. This effec t appears to be through interactions with Pit-1 and also by stabilizin g the mRNA. Somatostatin (SRIF) does not alter GH transcript levels in either tilapia or rainbow trout, although it may alter GH synthesis b y modulation of translation. Gonadal steroids appear to have different ial effects on the transcription of the beta subunits. In tilapia, tes tosterone (T) elevates I beta mRNA levels in cells from immature or ea rly maturing fish (in low doses), but depresses them in cells from lat e maturing fish and is ineffective in cells from regressed fish. Simil ar results were seen in early recrudescing male coho salmon injected w ith T or E-2. T or E-2 administered in vivo has dramatic stimulatory e ffects on the II beta transcript levels in immature fish of a number o f species, while less powerful effects are seen in vitro. A response i s also seen in cells from early maturing rainbow trout or tilapia, or regressed tilapia, but not in cells from late maturing or spawning fis h. These results are substantiated by the finding that the promoter of the salmon II beta gene contains several estrogen responsive elements (EREs) which react and interact differently when exposed to varying l evels of E-2. In addition, activator protein-1 (AP-1) and steroidogeni c factor-1 (SF-1) response elements are also found in the salmon II be ta promoter; the AP-1 site is located close to a half ERE, while the S F-1 acts synergistically with the E-2 receptor. The mRNA levels of bot h AP-1 and SP-1 are elevated, at least in mammals, by GnRH, suggesting possible sites for cross-talk between GnRH and steroid activated path ways. Reports of the effects of T or E-2 on GH transcription differ. N o effect is seen in vitro in pituitaries of tilapia, juvenile rainbow trout or common carp, but T does increase the transcript levels in pit uitaries of both immature and mature goldfish. Reasons for these discr epancies are unclear, but other systemic hormones may be more instrume ntal than the gonadal steroids in regulating GH transcription. These i nclude T, which increases both GH mRNA levels and de novo synthesis (i n tilapia and common carp) and insulin-like growth factor-I (IGF-I) wh ich reduces GH transcript levels as well as inhibiting GH release. (C) 1998 Elsevier Science Inc. All rights reserved.