PITUITARY-HORMONES AS NEUROTROPHIC SIGNALS - ANOMALOUS HYPOPHYSIOTROPHIC NEURON DIFFERENTIATION IN HYPOPITUITARY DWARF MICE

Anterior pituitary hormones are known to exert dynamic negative feedba ck effects on their respective regulatory (''hypophysiotropic'') neuro ns in the hypothalamus. The purpose of this review is to present the e vidence for a theory that the effect of pituitary hormones on these hy pophysiotropic neurons is neurotrophic, extending beyond dynamic feedb ack to influence upon cell survival, phenotypic differentiation, and a xonal connectivity. To that end, the adult condition and the developme nt of hypophysiotropic neurons in mutant mice which lack pituitary gro wth hormone (GH) and prolactin (PRL) are presented as models of the ef fect of absent specific neurotrophic signals. The expression of the ne urohormones which inhibit PRL and GH secretion, dopamine (DA) and soma tostatin, respectively, is markedly reduced in the hypothalamus of the hypopituitary dwarf mouse, and this adult condition is the result of postnatal failure to develop or actual regression, which may include n euronal cell death. The deficit in DA may be reversed by PRL replaceme nt, but only if initiated at an identified critical postnatal period. Conversely, expression of the stimulatory GH-releasing hormone (GHRH) is markedly increased in the dwarf mouse hypothalamus. The loss of DA and the increase in GHRH occur in the same hypothalamic area, suggesti ng neuronal phenotypic plasticity in response to absence of pituitary feedback signals. The axonal terminations of extant GH- and PRL-regula ting neurons in external median eminence appear to be reduced, suggest ing that pituitary signals are required for appropriate axonal guidanc e during development, even though an endocrine vascular route interven es between these regulatory neurons and their target secretory cells. The collective observations indicate that GH and PRL may be regarded a s neurotrophic factors for their respective regulatory neurons in the hypothalamus.