Evidence for a Possible Dopaminergic Control of Pituitary Alpha-MSH during Ontogenesis in Mice

Abstract

This study was aimed at determining the α-MSH and ACTH contents of the neurointermediate lobe (NIL) of the mouse hypophysis during ontogenesis, as well as the ability of the gland, incubated in a perfusion system, to respond to dopamine (DA) and high potassium (K⁺). We showed that: (1) the NIL content of α-MSH exhibited a biphasic pattern of evolution, characterized by a dramatic increase appearing between postnatal days 3 and 5. By contrast, NIL ACTH content followed a completely different pattern of evolution; (2) both DA and high K⁺ reversibly inhibited MSH release from superfused NIL, the latter effect being more pronounced with the use of pituitaries from 7-day-old than from 1-day-old mice; (3) the inhibitory influence of high K⁺ was impaired by haloperidol pretreatment. From these data, as well as from morphological observations, it appears that functional DA receptors seem to be present on melanotrophs of the developing hypophysis in mice and that the increase in α-MSH in IL cells observed shortly after birth may result from the onset of inhibitory influence exerted by dopaminergic innervation on hormonal secretion. This view, however, does not preclude possible effects of other hypothalamic releasing and/or inhibiting factors.

Early Postnatal Development of Pituitary Intermediate Lobe Control in the Rat by Dopamine Neurons

“…Though binding density is relatively low 2 days after birth, dopamine caused an inhibition of MSH release which was at least as great as that from older neuroin termediate lobes. A similar early postnatal responsiveness to dopamine as also been reported for the mouse pituitary [43]. The amount of MSH released spontaneously increases mar kedly through development.…”

“…In mice, Schmitt el al. [43] described a continuous slow rise of serum alpha-MSH levels from day 2 after birth. In neither study was there evidence for circulat ing MSH in the fetus.…”

Early loss of the retinoblastoma gene is associated with impaired growth inhibitory innervation during melanotroph carcinogenesis in Rb+/- mice.

“…Similarities between the length of an initiation-prone developmental window and period of time required for the development of Rb-negative EAPs strongly indicates loss of the R b gene as the initiation event of melanotroph carcinogenesis. Proliferation and maturation of melanotrophs are negatively controlled by hypothalamic dopaminergic innervation projected from the neural lobe during first days of the postnatal development (Schmitt et al 1981;Davis et al 1984;Hindelang et al 1990;Gary and Chronwall 1992;Rene et al 1993). The possibility that primary R b inactivation occurs in regulatory hypothalamic neurons is, however, unlikely.…”

“…A series of studies based on pituitary stalk transections, pharmacological modifications of dopamine receptor activation, and ontogenetic correlations has demonstrated tonic inhibitory effects of dopaminergic innervation on melanotroph proliferation. Dopaminergic innervation also inhibits the synthesis and secretion, respectively, of POMC and its melanotrophspecific cleavage products (Schmitt et al 1981;Rene et al 1993). During the first days of postnatal development, dopaminergic innervation appears at the border between the neural and intermediate lobes, expands in a gradientlike fashion, and soon becomes evenly distributed around cells (Schmitt et al 1981;Davis et al 1984;Gary and Chronwall 1992;Rene et al 1993).…”

“…Dopaminergic innervation also inhibits the synthesis and secretion, respectively, of POMC and its melanotrophspecific cleavage products (Schmitt et al 1981;Rene et al 1993). During the first days of postnatal development, dopaminergic innervation appears at the border between the neural and intermediate lobes, expands in a gradientlike fashion, and soon becomes evenly distributed around cells (Schmitt et al 1981;Davis et al 1984;Gary and Chronwall 1992;Rene et al 1993). This neural network ensures a mature state of hormonal synthesis, processing, and secretion by PND 60 (Tong and Pelletier 1990).…”