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Differential Effect of Age on Transforming Growth Factor-ß1 Inhibition of Prolactin Gene Expression Versus Secretion in Rat Anterior Pituitary Cells¹

Faculty of Medical Technology (S.-K.T., T.-C.L.), Institute of Biochemistry (S.-K.T., F.-F.W.), Institute of Physiology (H.-F.P., T.-C.L.), and Institute of Biotechnology in Medicine (T.-C.L.), National Yang-Ming University, Shih-Pai, Taipei, Taiwan, Republic of China

Address all correspondence and requests for reprints to: Dr. Tsuei-Chu Liu, Faculty of Medical Technology/Institute of Biotechnology in Medicine, National Yang-Ming University, Shih-Pai, Taipei 112, Taiwan, Republic of China. E-mail: tcliu{at}ym.edu.tw

Transforming growth factor-ß1 (TGF-ß1) synthesized in the pituitary may act as an autocrine/paracrine regulator of lactotrope function. We examined the effects of TGF-ß1 on PRL messenger RNA (mRNA), PRL synthesis, and PRL secretion in cultured anterior pituitary (AP) cells from rats at different ages. APs excised from ovariectomized female Sprague-Dawley rats, either young (2–3 months old; average serum PRL: 9 ng/ml), middle-aged (11–12 months old; average serum PRL: 133 ng/ml), or old (24 months old; average serum PRL: 159 ng/ml), were dispersed and cultured for 5 days. Then, cells were washed and challenged with increasing doses of TGF-ß1 (0–100 ng/ml) for 1–48 h in serum-free medium. Northern blot analysis showed an increase in basal PRL mRNA levels, and a decrease in responsiveness to TGF-ß1 with age. TGF-ß1 suppressed PRL mRNA in a dose- and time-dependent manner in cells from young rats. Maximum inhibition was observed at 0.5–1 ng/ml of TGF-ß1. At 0.5 ng/ml TGF-ß1, significant reduction in PRL mRNA was detected at 6 h, and maximum inhibition was observed at 12–48 h post TGF-ß1 incubation. Cells from middle-aged rats were less responsive to TGF-ß1, whereas cells from old rats did not seem to respond under our experimental conditions. In addition to its effect on PRL mRNA in young AP cells, TGF-ß1 dose dependently inhibited the rate of PRL synthesis, as indicated by reduced [³⁵S]methionine incorporation into immunoprecipitated PRL. Responsiveness of PRL synthesis to TGF-ß1 inhibition also decreased with age; however, significant inhibition by TGF-ß1 on PRL synthesis could still be observed in old AP cells. Analysis by RIA demonstrated that young AP cells produced lower levels (15 µg/10⁶ cells·24 h) of PRL in culture medium than old AP cells (32 µg/10⁶ cells·24 h). TGF-ß1 decreased medium PRL levels in old AP cells as efficaciously as in young AP cells. Significant reduction in medium PRL secreted by young AP cells was observed at 3 h when changes in both PRL mRNA and PRL synthesis were not evident. Taken together, our data suggest that TGF-ß1 affects PRL production at multiple levels. Moreover, its inhibition on PRL synthesis and mRNA expression, but not on PRL secretion, is age-related. Thus, TGF-ß1 may play an important role in regulating lactotrope function during aging.

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