GONADAL-STEROID REGULATION OF SUBSTANCE-P (SP) AND SP-ENCODING MESSENGER RIBONUCLEIC-ACIDS IN THE RAT ANTERIOR-PITUITARY AND HYPOTHALAMUS

Substance P-like immunoreactivity (SP-LI) is present in the rat anterior pituitary (AP) and in hypothalamic neurons that may be involved in the control of AP secretion and/or reproductive function. The presence of multiple SP- encoding mRNAs and tachykinin peptides and their regulation by steroid hormones were examined in APs and hypothalami from normal, gonadectomized, and steroid-treated male and female rats. SP-encoding mRNAs were identified by nuclease protection assays of RNA, and tachykinin peptides were identified by combined HPLC-RIA of tissue extracts. β- and γ-preprotachykinin (PPT) mRNAs and SP, neurokinin A, and neuropeptide γ peptides were identified in the AP. The α-, β-, and γ. PPT mRNAs and SP, neurokinin A, neuropeptide γ, neuro-peptide K, and neurokinin B peptides were present in hypothalamic tissue. Previous studies have established that in the AP, SP is differentially regulated by gonadal steroids; estrogen decreases and androgen increases AP SP. Steroid effects were further analyzed in experiments using RIAs to measure SP levels in the AP and median eminence (ME) of steroid- and oil-treated gonadectomized rats. To assess whether steroids alter steady state PPT mRNA levels and presumably SP synthesis in these tissues, potential effects on AP and hypothalamic SP-encoding mRNAs were determined. Ovariectomized rats treated for 10 days with estradiol benzoate showed a 50% decrease in AP SP and a 90% decrease in AP β- and γ-PPT mRNAs compared to ovariectomized oil-treated controls. Estradiol benzoate replacement had no effect on SP levels in the isolated ME, but did cause a 50% increase in α-, β-, and γPPT mRNAs in the hypothalamus. Although there was no significant effect of testosterone propionate on AP SP levels in castrated males, 10 days of testosterone propionate replacement did cause a significant increase in β- and γPPT mRNAs in the AP. No androgen effects were seen on either ME SP or hypothalamic SP-encoding mRNAs. These data demonstrate that estrogen up-regulates SP-encoding mRNAs in the hypothalamus, whereas it down-regulates SP- encoding mRNAs in the pituitary. These results implicate SP and other tachykinins derived from the SP gene as steroidregulated modulators of AP secretion and possibly reproductive function. © 1990 by The Endocrine Society.