Physiologically Significant Inhibitory Hypothalamic Action of Substance P on Prolactin Release in the Male Rat

Abstract

To evaluate a possible physiological role of endogenous substance P (SP) in the control of prolactin (PRL) release, conscious adult male rats were given injections of a specific antiserum against SP (anti-SP) into the third ventricle (3 µl) or intravenously (0.5 ml). Third-ventricular injection of anti-SP induced a significant increase in plasma PRL levels when compared to values in control animals injected with normal rabbit serum (p < 0.02). Plasma PRL concentrations were significantly elevated within 2 h after injection of antiserum and remained elevated for the 4-hour duration of the experiment. In contrast, injections of large doses of anti-SP intravenously had no effect on plasma PRL levels. In order to confirm the effect of SP itself, synthetic SP was injected intravenously and intraventricularly. Opposite effects of SP on PRL release were observed after intravenous and intraventricular injections of low or high doses of the peptide. A lower dose of SP (10 ng, 7.42 pmol) injected into the third ventricle suppressed the release of PRL (p < 0.01), whereas higher doses (1 µg, 0.74 nmol, or 5 µg, 3.71 nmol) had a stimulatory effect on PRL release (p < 0.01). Similarly, a low dose of SP (0.1 µg, 0.07 nmol) injected intravenously lowered plasma PRL (p < 0.05). Large doses of intravenous SP (50 µg, 37.1 nmol) dramatically stimulated PRL release (p < 0.001). To evaluate a possible direct action of SP on PRL release from the anterior pituitary, the peptide was incubated with dispersed anterior pituitary cells for 1 h. The release of PRL from incubated anterior pituitary cells was not affected at any dose of synthetic SP tested (10^–9–10^–6M. These data indicate that in the male rat endogenous SP is a physiologically significant inhibitor of basal release of PRL, via a hypothalamic action, although higher, presumably pharmacological doses of SP stimulate the release of this hormone also via hypothalamic action.

Tumour Necrosis Factor Alpha, Interferon Gamma and Substance P Are Novel Modulators of Extrapituitary Prolactin Expression in Human Skin

“…Given that substance P is a key mediator of neurogenic skin inflammation [70], and may partially explain the effects of psychological stress on hair growth in alopecia areata and telogen effluvium [33], it is interesting to note that substance P decreased PRL IR. This is well in line with similar substance P effects reported on pituitary PRL production in rodents [71].…”

Substance P: multifunctional peptide in the hypothalamo-pituitary system?

“…Injection of SP into the third ventricle (Vijayan & McCann, 19796) or into the medial preoptic area (Picanco-Diniz, Valenca, Franci & Antunes- Rodrigues, 1990) resulted in increased concentrations of prolactin in rat plasma, and the former route of administration was also effective in primates (Eckstein, Wehrenberg, Louis et al 1980). However, recent work has demon¬ strated that, although higher doses of SP given intraventricularly can indeed stimulate the release of prolactin, inhibition can be induced by lower doses (Arisawa, Snyder, Yu et al 19906), and the same paradoxical pattern of prolactin response was observed following low or high intravenous doses of SP. Since it is improbable that SP can cross the blood-brain barrier, the evidence so far is weighted towards SP modulating the release of prolactin directly from anterior pituitary lactotrophs, although no increased plasma concentrations of pro¬ lactin following intravenous SP were observed in sheep (Thomas, Cummins, Griffin & Clarke, 1988).…”

Substance P enhances the proliferation of rat anterior pituitary cells in vitro

“…Being stored in the secretroy vesicles of these cells [3], SP is synthesized de novo as verified by constitutive expression of preprotachykinin A mRNAs encoding the precursors of SP [4]. Moreover, the anterior pituitary cells bear specific membrane receptors of NK-1 type for SP [5,6], which justifies the widely observed yet diverse effects of SP on hormonal secretion from the anterior pituitary [7].…”