Abstract
Glandular kallikrein (GK, a trypsin-like serine protease) exhibits estrogen induction and dopamine repression in rat pituitary lactotrophs. Steroid induction may reflect primary actions to increase selectively the synthesis of specific proteins, or may be part of broad cellular responses secondary to steroid-induced phenotype transitions. This study examined the cellular mechanisms underlying estrogen and dopaminergic control of lactotroph GK using a quantified immunocytochemical approach. Pituitaries from ovariectomized rats exhibited little GK staining. Estradiol treatment for 10 days produced dose-dependent increases in pituitary mass, the percentage of lactotrophs (indicating lactotroph proliferation) and the percentage of GK-positive cells. Also, GK staining intensity was dependent upon estradiol dose, increasing 4-fold between 5 μg and 50 μg/48 h. Dopamine receptor blockade with haloperidol (2.5 mg/kg/24 h) elicited weak GK immunostaining in 46% of the lactotrophs in the absence of estradiol, and markedly potentiated GK staining intensity elicited with low but not high doses of estradiol. The results suggest that GK induction is a primary estrogen effect, and is not secondary to a phenotype transition: the induction is enhanced by estrogen-induced lactotroph proliferation. Dopaminergic systems strongly inhibit GK induction by low estradiol levels. This dopaminergic modulation may shift the induction of lactotroph GK to physiological events associated with high estradiol levels or low dopaminergic tone.
Similar content being viewed by others
References
Anthony PK, Stoltz RA, Puci ML, Powers CA (1993) The 22K variant of rat prolactin: evidence for identity to prolactin 1–173, storage in secretory granules, and regulated release. Endocrinology 132:806–814
Ashley PL, MacDonald RJ (1985) Kallikrein-related mRNAs of the rat submaxillary gland nucleotide sequences of four distinct types including tonin. Biochemistry 24:4512–4520
Chao J, Chao L (1988) Identification of latent tissue kallikrein prolactin and growth hormone secretion in GH3 pituitary cells using modified radioimmunoassay. Mol Cell Endocrinol 55:21–31
Chao J, Chao L, Swain Ch, Tsai J, Margolius H (1987) Tissue kallikrein in rat brain and pituitary: regional distribution and estrogen induction in the anterior pituitary. Endocrinology 120:475–482
Chretien M (1977) Action of testosterone on the differentiation and secretory activity of a target organ: the submaxillary gland of the mouse. Int Rev Cytol 50:333–396
Clements JA (1989) The glandular kallikrein family of enzymes: tissues-specific expression and hormonal regulation. Endocr Rev 10:393–419
Clements J, Fuller P, McNally M, Nikolaidis J, Funder J (1986) Estrogen regulation of kallikrein gene expression in the rat anterior pituitary. Endocrinology 119:268–273
Dannies PS (1985) Control of prolactin production by estrogens. In: Litwack G (ed) Biochemical Actions of Hormones, vol 12. Academic Press, New York, pp 289–310
Hatala MA, Powers AC (1987) Dynamics of estrogen induction of glandular kallikrein in the rat anterior pituitary. Biochim Biophys Acta 926:258–263
Hatala MA, Powers CA (1989) Biochemical study of the subcellular localization of the estrogen-induced pro-glandular kallikrein in the rat anterior pituitary. Neuroendocrinology 49:537–544
Jones TH, Figueroa CD, Smith C, Cullen DR, Bhoola KD (1990) Characterization of a tissue kallikrein in human prolactin-secreting adenomas. J Endocrinol 124:327–331
Kitagawa A, Kizuki K, Moriya H, Kudo M, Noguchi T (1990) Kallikrein-and prolactin-producing cells in the rat anterior pituitary are the same. J Biochem (Tokyo) 108:971–975
Kizuki K, Kitagawa A, Takahashi M, Moriya H, Kudo M, Noguchi T (1990) Immunohistochemical localization of kallikrein within the prolactin-producing cells of the rat anterior pituitary. J Endocrinol 127:317–323
Mason A, Evans B, Cox D, Shine J, Richards R (1983) Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides. Nature 303:300–307
Maurer RA, Notides AC (1987) Identification of an estrogen-responsive element from the 5′-flanking region of the rat prolactin gene. Mol Cell Biol 7:4247–4254
Powers CA (1986a) Trypsin activation, partial characterization, and distribution of kallikrein-like and thrombin-like proteases in the neurointermediate lobe of the rat pituitary. J Neurochem 47:145–153
Powers CA (1986b) Anterior pituitary glandular kallikrein trypsin activation and estrogen regulation. Mol Cell Endocrinol 46:163–174
Powers CA (1987) Elevated glandular kallikrein in estrogen-induced pituitary tumors. Endocrinology 120:429–431
Powers CA, Hatala MA (1986) Dopaminergic regulation of the estrogen-induced glandular kallikrein in the rat anterior pituitary. Neuroendocrinology 44:462–469
Powers CA, Hatala MA (1990) Prolactin proteolysis by glandular kallikrein; in vitro reaction requirements and cleavage sites, and detection of processed prolactin in vivo. Endocrinology 127:1916–1927
Powers CA, Nasjletti A (1983) A kininogenase resembling glandular kallikrein in the rat pituitary pars intermedia. Endocrinology 112:1194–1200
Powers CA, Nasjletti A (1984) A major sex difference in kallikreinlike activity in the rat anterior pituitary. Endocrinology 114:1841–1844
Pritchett DB, Roberts JL (1987) Dopamine regulates expression of the glandular-type kallikrein gene at the transcriptional level in the pituitary. Proc Natl Acad Sci USA 84:5545–5549
Raymond V, Beaulieu M, Labrie F, Boisser J (1978) Potent antidopaminergic activity of estradiol at the pituitary level on prolactin release. Science 200:1173–1175
Sternberger LA (1979) Immunocytochemistry, 2nd edn. Wiley, New York
Toumisto J, Mannisto P (1985) Neurotransmitter regulation of anterior pituitary hormones. Pharmacol Rev 37:249–332
van Leeuwen BH, Penschow JD, Richards RI (1987) Cellular basis for the differential response or mouse kallikrein genes to hormonal induction. EMBO J 6:1705–1713
Vio CP, Figueroa CD (1985) Subcellular localization of renal kallikrein by ultrastructural immunocytochemistry. Kidney Int 28:36–42
Vio CP, Silva R, Powers CA (1989) Immunocytochemical identification of glandular kallikrein in the rat anterior pituitary. Adv Exp Med Biol 247:183–188
Vio CP, Roa JP, Silva R, Powers CA (1990) Localization of immunoreactive glandular kallikrein in lactotrophs of the rat anterior pituitary. Neuroendocrinology 51:10–14
Waterman ML, Adler S, Nelson C, Greene GL, Evans RM, Rosenfeld MG (1988) A single domain of the estrogen receptor confers deoxyribonucleic acid binding and transcriptional activation of the rat prolactin gene. Mol Endocrinol 2:14–21
Wines DR, Brady JM, Pritchett DB, Roberts JL, MacDonald RJ (1989) Organization and expression of the rat kallikrein gene family. J Biol Chem 264:7653–7662
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Roa, J.P., Powers, C.A., Silva, R. et al. Cellular mechanisms of estrogen-and dopamine-induced control of glandular kallikrein in the anterior pituitary of the rat. Cell Tissue Res 274, 421–427 (1993). https://doi.org/10.1007/BF00314538
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00314538