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 β subunit of the GtH I being found in close proximity to the somatotrophs, while the IIβ cells are more peripheral. In several species the GtH β subunits are expressed at varying levels throughout the reproductive cycle, the Iβ dominating in early maturing fish, after which the IIβ becomes predominant. This suggests differential control of the β 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 plasma growth hormone (GH) levels increase. In a number of species, GnRH elevates either the Iβ or the IIβ mRNA levels, depending on the reproductive state of the fish. In tilapia, the GnRH effect on the IIβ 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 direct activation of PKC are ineffective in altering GH mRNA in tilapia pituitary cells. Dopamine (DA) does not alter IIβ transcript levels in cultured tilapia pituitary cells, but increases GH mRNA levels in both rainbow trout and tilapia, in a PKA-dependent manner. This effect appears to be through interactions with Pit-1 and also by stabilizing the mRNA. Somatostatin (SRIF) does not alter GH transcript levels in either tilapia or rainbow trout, although it may alter GH synthesis by modulation of translation. Gonadal steroids appear to have differential effects on the transcription of the β subunits. In tilapia, testosterone (T) elevates Iβ mRNA levels in cells from immature or early maturing fish (in low doses), but depresses them in cells from late maturing fish and is ineffective in cells from regressed fish. Similar results were seen in early recrudescing male coho salmon injected with T or E₂. T or E₂ administered in vivo has dramatic stimulatory effects on the IIβ transcript levels in immature fish of a number of species, while less powerful effects are seen in vitro. A response is also seen in cells from early maturing rainbow trout or tilapia, or regressed tilapia, but not in cells from late maturing or spawning fish. These results are substantiated by the finding that the promoter of the salmon IIβ gene contains several estrogen responsive elements (EREs) which react and interact differently when exposed to varying levels of E₂. In addition, activator protein-1 (AP-1) and steroidogenic factor-1 (SF-1) response elements are also found in the salmon IIβ promoter; the AP-1 site is located close to a half ERE, while the SF-1 acts synergistically with the E₂ receptor. The mRNA levels of both AP-1 and SP-1 are elevated, at least in mammals, by GnRH, suggesting possible sites for cross-talk between GnRH and steroid activated pathways. Reports of the effects of T or E₂ on GH transcription differ. No effect is seen in vitro in pituitaries of tilapia, juvenile rainbow trout or common carp, but T does increase the transcript levels in pituitaries of both immature and mature goldfish. Reasons for these discrepancies are unclear, but other systemic hormones may be more instrumental than the gonadal steroids in regulating GH transcription. These include T₃ which increases both GH mRNA levels and de novo synthesis (in tilapia and common carp) and insulin-like growth factor-I (IGF-I) which reduces GH transcript levels as well as inhibiting GH release. Copyright (C) 1998 Elsevier Science Inc.