Masayoshi Arisawa

Stimulatory Role of Substance P on Gonadotropin Release in Ovariectomized Rats

Substance P (SP) has been shown to be present in the hypothalamus and anterior pituitary. To evaluate a possible physiological role of endogenous SP in the control of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, specific antiserum against SP (anti-SP) was injected intraventricularly (3 microliters into the third ventricle) or intravenously (50 or 200 microliters) into conscious, ovariectomized (OVX) rats. Third ventricular injection of the antiserum induced a significant decrease in both plasma LH and FSH levels when compared to values in control animals injected with normal rabbit serum (p less than 0.01 and p less than 0.025, respectively). The effect was observed within 10 mi and levels remained suppressed for 60 min. In contrast, intravenous injection of large doses of anti-SP had no effect on the release of both hormones. In order to confirm the stimulatory effect of SP itself, synthetic SP was injected intravenously and intraventricularly into estrogen-primed (E-primed), OVX rats. Synthetic SP dramatically stimulated LH release, but not FSH release when injected either intravenously or intraventricularly at doses of 10 and 50 micrograms (p less than 0.001, p less than 0.005 vs. control, respectively). To investigate any direct action of SP on gonadotropin release from the anterior pituitary gland, synthetic SP was incubated with dispersed anterior pituitary cells harvested from E-primed OVX rats. SP did not affect the release of gonadotropins in vitro. These results indicate that endogenous hypothalamic SP exerts a tonic stimulatory hypothalamic control of basal gonadotropin release in OVX rats.

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

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 microliters) 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 less than 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 less than 0.01), whereas higher doses (1 microgram, 0.74 nmol, or 5 micrograms, 3.71 nmol) had a stimulatory effect on PRL release (p less than 0.01). Similarly, a low dose of SP (0.1 microgram, 0.07 nmol) injected intravenously lowered plasma PRL (p less than 0.05). Large doses of intravenous SP (50 micrograms, 37.1 nmol) dramatically stimulated PRL release (p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the gonadotropin-releasing hormone associated peptides (GAP) on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in vivo.

Six peptide sequences residing between basic amino acid residues in GAP were tested for effects on the release of FSH, LH and PRL in vivo in ovariectomized, estrogen-progesterone-primed (OEP) rats. Synthetic GAP peptides (1-13, 1-23, 15-23, 25-36, 38-53 and 41-53) were injected intravenously (IV) into conscious OEP rats and plasma levels of FSH, LH and PRL were measured by RIA. The activity of GAP peptides in the control of PRL was further examined in ether-stressed male rats which were injected IV with GAP peptides just prior to a 1-min etherization. GAP(1-13) significantly stimulated FSH release at doses of 1, 10 and 100 micrograms, whereas it stimulated LH release only at the highest dose of 100 micrograms. GAP(1-23) elevated plasma levels of FSH and LH only at a dose of 100 micrograms. The other 4 peptides had no effect on the release of gonadotropins. Of these 6 peptides, only GAP(1-13) partially lowered the plasma levels of PRL at the high dose of 100 micrograms in OEP rats, but it had no effect on the ether-induced PRL surge at doses of 10 and 100 micrograms. In conclusion, both GAP(1-13) and GAP(1-23) stimulate FSH and LH release in vivo; these 2 peptides are much less potent in stimulating gonadotropin release than is LHRH. GAP(1-13) exerts a preferential FSH-releasing activity, but its PRL-inhibiting activity is minimal.

Effect of substance P on thyrotropin secretion from the pituitary gland in the rat.

The role of substance P (SP) on thyrotropin (TSH) secretion was investigated in ovariectomized (OVX) female, estrogen-primed OVX, and normal male rats. Third ventricular administration of SP induced a significant increase in plasma TSH levels when compared to control animals in E-primed OVX rats (p less than 0.001). The plasma TSH levels increased in a dose-related manner and reached maximum levels at 10 min after injection. In contrast, intraventricularly injected SP failed to alter plasma TSH levels in both OVX rats and normal male rats. Intravenous administration of SP dramatically stimulated TSH release in E-primed OVX rats (p less than 0.001), whereas SP had no effect on the release of TSH when injected in OVX rats and normal male rats. To investigate any direct action of SP on TSH release from the anterior pituitary gland, synthetic SP was incubated with dispersed anterior pituitary cells harvested from E-primed OVX rats and normal male rats. SP, in the dose range between 10(-8) M and 10(-6) M, failed to alter the release of TSH into the culture medium in vitro. These findings indicate that SP has a stimulatory role in the control of TSH release by an action on the hypothalamus but only in estrogen-primed rats.