Pituitary Receptors during Development in the Rat. I. TRH Binding Capacity

Abstract

SummaryIn order to study the role of thyroid releasing hormone (TRH) in the control of thyroid stimulating hormone (TSH) secretion during the neonatal period, we measured the binding of [3H]-TRH to pituitary homogenate of rats at various stages of development. In 2-day-old animals, the number of l3H]-TRH binding sites were similar to that of adult male animals (23 + 8 fmole/mg protein versus 21 + 7 fmole/mg protein, respectively). Between 5-21 days of age, the number of i3HJ-TRH binding sites was significantly higher than that of adult animals (P < 0.01). Hypothyroidism induced a Zfold increase in the number of [3H]-TRH binding sites in all the age groups studied. This effect was reversed by administration of L-T4 (0.4 pg/g body weight for 3 days). These studies thus indicate that TRH biding sites are present during the neonatal period in the rat and suggest that TRH may be an important modulator of TSH secretion during this period in the rat and that these effects are mediated by postreceptor mechanisms. AbbreviationsCMC, carboxy methyl cellulose GH3, growth hormone PTU, propylthiouracil TRH, thyroid releasing hormone TSH, thyroid stimulating hormoneThe hypothalamo-pituitary-thyroid axis develops postnatally in the rat (1 1). Hypothalamic TRH concentrations as well as pituitary and serum TSH levels increase gradually after birth and reach adult values by the second wk of postnatal life. In the rat, the secretion of TSH is dependent upon the release of the hypothalamic hormone TRH. TRH binds to specific receptor sites on the external surface of the plasma membrane of thyrotrophs and/or mamrnatrophs and activates adenylyl cyclase with elevation of intracellular levels of cyclic AMP leading to the activation of protein kinase, phosphorylation of protein substrates and modifications in the secretion of TSH and prolactin (16). TRH receptor sites have now been characterized in bovine and rat pituitary gland (7, 16), as well as in thyrotropic-pituitary tumor cells (19).Previous experiments have shown that in the adult animal, the level of pituitary TRH receptor is modulated by both estrogens and thyroid hormones (7). Hypothyroidism induces a significant increase in the number of TRH receptors, whereas administration of thyroid hormones leads to a progressive decline in the levels of TRH receptors (7). Previous experiments have suggested that TRH was not the modulator of TSH secretion during the neonatal period. Tonooka et al. (21) reported that serum TSH concentrations in encephalectomized fetus was markedly elevated when pregnant rats were fed PTU and that hypothalamic lesions in these PTU-fed pregnant rats did not prevent the TSH rise in the fetus. Theodoropoulos et al. (20) treated neonatal hypothyroid rats with TRH antiserum and found that this treatment was ineffective in decreasing serum TSH concentrations before the tenth day of life. We have recently observed that exogenous administration of TRH during the neonatal period leads to a significant increase in serum TSH concentration, which can be impaired in a ...

Thyroid Hormone Regulation of TRH mRNA Levels in Rat Paraventricular Nucleus of the Hypothalamus Changes during Ontogeny

“…In a recent study with the use of in situ hybridization histochemistry, a highly sensitive and anatomically specific form of analysis, TRH mRNA was seen in other brain regions prior to EI6 but TRH localized in the PVN was first detected at E 16 [5]. Once present, immunoreactive TRH levels in hypothalami increase until 18 days after birth [17] or young adulthood [6] as did TRH mRNA levels in the PVN [5]. In the present study, TRH mRNA was noted in the PVN at E l6, levels increased until 7d after birth and appeared to plateau through young adulthood.…”

“…TRH administered to newborn euthyroid [8,9] and hypo thyroid rats [10] stimulates TSH secretion and this response in creases at 5-10 days after birth [8][9][10]. Also, TRH receptors have been described in the pituitary as early as 2 days after birth [17,19). Therefore, the presence of thyrotroph receptors for TRH as well as the ability of the thyrotroph to respond to exoge nous TRH supports the concept that the lack of TSH response to endogenous TRH in the early perinatal period is hypotha lamic rather than pituitary in origin.…”

Influence of Age on the Control of Thyrotropin Secretion by Thyrotropin-Releasing Hormone in the Male Rat

“…Moreover, the low circulating levels of thyroid hormones -Tt and Tj -in old rats may also contribute to the increased density ofTRH receptors, since Tj is known to exert an inhibitory control on pituitary TRH receptors [10, 31]. Indeed, in the developing rat, a progressive decrease in the density of pituitary TRH receptors is observed [3,16] which is concomitant with increases in plasma T3 and hypo thalamic TRH concentrations [35,41].As regards TRH in the anterior pituitary gland, our fin ding of an increased concentration of the peptide in old rats may appear unexpected in view of the reduced level ofTRH detected in the median eminence. However, it may reflect a greater internalization ofTRH in pituitary cells secondary to the increased number of pituitary receptors for TRH found in old animals.…”

Distribution, Cellular Localization, and Ontogeny of Preprothyrotropin-Releasing Hormone-(160–169) (Ps4)-Binding Sites in the Rat Pituitary1

“…Previous studies have shown that TRH receptors are also expressed at birth and that their density increases postnatally (41,42). Concurrently, the number of TRH-producing neurons in the paraventricular nucleus increases during the first week of life (43,44).…”