Ontogeny of the hypothalamic-pituitary (growth hormone)-insulin-like growth factor-I axis in birds

Ontogeny of the Hypothalamic-Pituitary (Growth Hormone)-Insulin-Like Growth Factor-I Axis in Birds'

COLIN G. SCANES2

SYNOPSIS. The ontogeny of the hypothalamic-pituitary growth hormone (GH)-insulin-like growth factor- (IGF-) I axis particularly in birds is considered. Moreover, the ontogeny of IGF-II and IGF-binding proteins (IGF-BPs) are also discussed. Models for the axis in fetal and postnatal mammals, embryonic and posthatching birds, together with nutritionally-deprived mammals and birds are suggested as are the evolutionary changes in the axis.

The hypothalamo-pituitary growth hormone (GH)-insulin-like growth factor-I (IGF-I) growth axis is well defined in mammals and birds at different stages of development and physiological states (Fig. 1). The axis consists of hypothalamic releasing factors [GH-releasing factors (GHRF) stimulating GH release and somatostatin inhibiting GH release together with another GH secretagogue in birds, thyrotropin releasing hormone (TRH)], GH, IGF-I (and possibly IGF-II), and IGF binding proteins (IGFBPs) together with the respective receptors. This paper will consider the ontogeny of GH, IGF-I and the IGFBPs in birds including changes in circulating concentrations, roles during development, and the control system. In addition, comparative and evolutionary aspects will be briefly considered. By convention or tradition, the developing bird is referred to as an embryo during the entire period from fertilization through incubation of the egg to hatching. This can be viewed as equivalent to the period in utero or of gestation in mammals. Thus the avian embryo may be analogous to either the embryo or fetus in mammals.

GROWTH HORMONE

In the chicken, plasma concentrations show a distinct monophasic ontogenic profile. This is characterized by increases in late embryonic development and early posthatch growth, an early-to-mid-growth peak and a decline to low levels of adulthood (Harvey et al., 1979; Scanes and Harvey, 1981). Similar profiles are found in all avian species examined, these being of diverse origins, including turkeys (Harvey et al., 1977), ring doves (Scanes and Balthazart, 1981), American kestrels (Lacombe et aL, 1993), Japanese quail and European starlings (Schew et al., 1996). The profile for pituitary GH mRNA levels during growth and development is very similar to those of circulating GH (McCann-Levorse et al., 1993; Kansaku et al., 1994). This would suggest a tight link between GH synthesis and release.

In mammals, somatotrophs develop early in gestation. The situation in birds is very different. Somatotrophs are not evident in the pituitary of the chick embryo until between day 10 and 12 of incubation, and at this time cells are sparse, small, and poorly developed (Malamed et aL, 1993; Porter et al., 1995a). Through the second half of embryonic development, somatotrophs increase in number, size, and in the number of GH-secreting granules (Malamed et al., 1993; Porter et al.,1995a). During mid and late stages of growth, there are declines in the proportion of somatotrophs and also in their ability to release GH (Malamed et aL, 1985; Reichardt, 1993).

The underlying mechanism for the increase in somatotrophs is not well established. In rats, somatotroph numbers are reported to be increased by the presence of glucocorticoids and insulin (Hemmings et al., 1988). In the chick embryo, glucocorticoid administration decreases the pituitary GH content (J. C. Gould and C. G. Scanes, unpublished observations). Moreover, chick embryo adenohypophyseal cells cultured in vitro do not respond to either releasing factors (e.g., GHRF, TRH) or insulin with any changes in the percentage of somatotrophs (Porter et al.,1995b). However, serum from 16 day chick embryos did greatly increase the percentage of somatotrophs with adenohypophyseal cells cultured in vitro (Porter et al., 1995b). This would clearly indicate that a blood-borne factor was responsible for somatotroph development.

In mammals, the activation of the GH gene is effected by the pituitary transcription activator Pit-1/GHF- 1. In the chick embryo, Pit-1/GHF-1 mRNA levels peak on day 15 of embryonic development when somatotroph proliferation/differentiation is proceeding rapidly (R. Choudhuri and C. G. Scanes, unpublished observations).

In the chick embryo, there are substantial numbers of GH receptors in the liver (Vanderpooten et al., 1991). It might be suggested that the increasing circulating concentrations of GH prior to hatching are elevating hepatic monodeiodination of thyroxine (T4) to triiodothyronine (T3) (Darras et al., 1990). In avian embryonic development, GH may have other roles including stimulating angiogenesis (Gould et al., 1995) and affecting bone growth. Moreover, a role for GH in the growth of the avian embryo is indicated by the reduction in growth in decapitated embryos and the effects of GH on various tissues (Thommes et al., 1992).

It is proposed that circulating concentrations of GH are maintained at low levels in the chick embryo as a protective measure. Growth hormone may have adverse effects on embryonic development. Although this notion is based on conjecture, there is some circumstantial evidence in its support.