Thomas L. Garthwaite

Age-Related Changes in Central Nervous System Beta-Endorphin and ACTH

Aging is associated with alterations in mood, thermoregulation, pain threshold, and stress response. Because these functions may be modulated by endogenous opiates, we measured immunoreactive ACTH with beta-endorphin in discrete brain areas and pituitary glands from rats aged 6 weeks (young), 6 months (mature), and 20-24 months (senscent). Beta-Endorphin and ACTH declined significantly with aging in the hypothalamus and corpus striatum. Beta-Endorphin and ACTH increased in the frontal lobe during early life; however, no change was noted after maturity. A discordant response with age was noted in the pituitary in that (ACTH did not change, while beta-endorphin increased early in life without change after maturity. Cerebellar tissue exhibited no immunoreactive ACTH or beta-endorphin. Age-related changes in brain and pituitary beta-endorphin and ACTH must be considered in the evaluation of the physiological aging process and when comparing studies of these neuropeptides.

Antisera to Vasoactive Intestinal Polypeptide Inhibit Basal Prolactin Release from Dispersed Anterior Pituitary Cells

Vasoactive intestinal polypeptide (VIP) has been identified in hypothalamic tissue, is secreted into hypophysial portal blood, and stimulates prolactin (PRL) release in vivo and in vitro. It has been proposed, therefore, that VIP is a physiologic PRL-releasing factor. In this study, we confirm that VIP stimulates PRL release from rat pituitary cells in vitro, and demonstrate that an anti-VIP antiserum blocks VIP-induced PRL secretion. Surprisingly, the anti-VIP antiserum inhibited basal PRL secretion from rat pituitary cells in 3 separate experiments. Data from these experiments were pooled, as the responses were similar, revealing basal PRL release of 10.7 +/- 1.3 ng rPRL/10(5) cells (X +/- SE), while anti-VIP antisera significantly inhibited release to 4.4 +/- 0.6 ng rPRL/10(5) cells (p less than 0.001). PRL release in incubates containing control non-immune sera did not differ from basal release, 8.1 ng rPRL/10(5) cells. A further control experiment was conducted wherein cells were incubated with an anti-ACTH antiserum, representing another hyperimmune serum, which had no effect on PRL secretion. These data suggest that VIP, in addition to its possible role as a hypothalamic-derived PRL-releasing factor, may play a role within the pituitary as a regulator of basal PRL secretion.

Running Elevates Plasma β-Endorphin Immunoreactivity and ACTH in Untrained Human Subjects

Abstract Twenty minutes of submaximal treadmill running was associated with an elevation in plasma levels of β-endorphin immunoreactivity (P < 0.02). This increase was greater in men (14.9 ± 3.4 fmole/ml) than women (2.6 ± 1.2 fmole/ml) (P < 0.05). Plasma levels of ACTH and growth hormone also increased after running. ACTH increased more in men (7.8 ± 1.1 fmole/ml) than in women (1.1 ± 0.44 fmole/ml) (P < 0.02). There was a similar growth hormone response in both sexes. No correlation can at this time be made with levels in the central nervous system. Changes in plasma levels of β-endorphin immunoreactivity may be responsible for some of the euphoria and analgesia anecdotally associated with running.

Evidence that Serotonin Stimulates a Prolactin-Releasing Factor in the Rat

Methanol extracts of rat plasma resulted in release of prolactin (PRL) from rat hemipituitaries in vitro with a linear log-dose relationship. This prolactin-releasing factor (PRF)-like activity was not altered in plasma from rats treated with bromocryptine or chlorpromazine despite significant suppression and stimulation of plasma PRL levels, respectively. Fluoxetine, a serotonin reuptake inhibitor, plus 5-hydroxytryptophan, the immediate precursor of serotonin, markedly stimulated both plasma PRL and plasma PRF-like activity. Neither fluoxetine, 5-hydroxytryptophan, nor the combination directly stimulated PRL release from rat pituitary tissue in vitro. We conclude that serotonergic stimulation augments PRL release via a PRF.

Central administration of motilin stimulates feeding in rats

Peripheral administration of motilin has been found to stimulate feeding behavior in rats. Since motilin immunoreactivity has been found in discrete brain sites, we tested the effect of motilin administered intracerebroventricularly on feeding in rats. Injection of 1 microgram of motilin significantly increased food consumption at 2 hours, 22 hours, and at 24 hours in animals tested either at or 2 hr prior to lights out. Motilin also significantly increased food consumption in animals maintained under continuous lights-on at 2 hours (488% of control), 22 hours (128% of control), and at 24 hours (140% of control).

Peripheral motilin administration stimulates feeding in fasted rats.

Although the physiologic function of the gastrointestinal hormone motilin remains uncertain, plasma levels of this peptide vary with migrating myoelectric complexes (MMCs) in the small intestine. In the fed state, both MMCs and plasma motilin are suppressed. During fasting, cyclical peaks of motilin in plasma occur at the same time as Phase III of the MMC cycle occurs in the duodenum. This dependence of motilin concentrations in plasma on the feeding state of the animal prompted an investigation of the effects of motilin on feeding behavior. Intraperitoneal injection of motilin into fasted, but not fed, rats stimulated eating in a dose dependent manner. A significant stimulation of feeding was seen at doses of 5 and 10 micrograms/kg. Sated rats did not eat whether injected with motilin or vehicle. The feeding response to motilin was blocked by prior injection of the rats with naloxone, naltrexone, or pentagastrin. The dose response suppression of food intake by naloxone was similar in fasted animals treated with motilin or vehicle. Motilin may function as a hunger hormone during periods of fasting.

Circulating corticotropin releasing factor-like activity in man.

Summary In order to investigate the possible existence of corticotropin releasing factor (CRF)-like activity in human plasma, methanol extracts of plasma were incubated with rat anterior pituitary tissue in vitro and ACTH release was determined. The extracts were reconstituted so that 1.0 ml was equivalent to 20 ml of original plasma, and the following doses in 5.0-ml incubation volumes elicited a stepwise increase in ACTH release: 100, 250, 500, and 750 μ1. The 250-, 500-, and 750-μl doses resulted in a linear log dose-response. Parallel experiments with 0.5, 1, 2, 5, and 10 rat hypothalamic equivalents in 5.0-ml incubation volumes resulted in a similar stepwise increase in ACTH release. Control experiments indicated a significantly greater ACTH release when pituitary tissue was incubated with methanol extracts of rat hy-pothalami in comparison to hypothalami added directly in vitro, validating the methanol extraction technique with a known source of CRF. Ultrafiltration experiments with the human plasma CRF-like activity suggest a molecular weight larger than 10,000 daltons.

Galactorrhea, Gynecomastia, and Hypothyroidism in a Man

Excerpt To the editor: Galactorrhea occurs rarely in men and most cases are reported in patients with prolactin-secreting pituitary tumors (1, 2). The occurrence of hyperprolactinemia and galactorr...