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Numerous studies have demonstrated that a variety of hormones have receptors and exert biologic actions on tissues of the immune system. Conversely, cytokines exert biologic actions on the endocrine system. This bidirectional interaction is likely involved in maintenance of physiological and immunologic homeostasis. This paper summarizes a variety of actions of growth hormone (GH), prolactin (PRL), insulin-like growth factor-I (IGF-I), glucocorticoids and thyroid hormones (TH) on the immune system. It then proceeds to put these actions into a hypothetical context whereby these hormones may mediate some changes in immune system function in response to environmental stimuli such as physical and emotional stress, nutritional deprivation and environmental temperature. In the first example, it is proposed that PRL secretion in response to stress may serve an immunomodulatory role in two ways. The first is by stimulating the immune system directly and the second is by dampening or reducing the degree to which glucocorticoids are secreted in response to stress. The second example suggests that the increase in GH secretion and reduced IGF-I secretion in response to protein/energy restriction may have two potential immunomodulatory actions. One action is a direct effect of GH on several components of the immune system. The other is the partitioning of nutrient use away from skeletal muscle growth and toward tissues of higher priority such as the immune system. The third example proposes that the increased secretion of TH during cold environmental temperatures not only increases basic metabolic rate, but also directly stimulates both primary and secondary lymphoid tissues. It is suggested, therefore, that these three hormones are involved in maintaining immune system homeostasis in response to environmental change.

The presence of growth hormone receptors (GHR) on sheep peripheral blood mononuclear (PBMN) cells was studied in two ways. The first was to directly measure specific GH-binding sites on PBMN cells drawn from lambs from birth to 5 months of age. The second was to measure the effect of GH on resting and interleukin-2 (IL-2)-activated PBMN cells in vitro and also the effect of other hormones such as prolactin (PRL), insulin-like growth factor-1 (IGF-1), and glucocorticoid. The specific binding of [125I]human GH (hGH) was low on PBMN cells but increased (P < 0.05) with age up to 5 months. Interestingly, serum concentrations of GH-binding protein also increased (P < 0.01) with age and were highly correlated (r = 0.89; P < 0.05) with the specific binding of GH to PBMN cells. The addition of ovine GH (oGH) to PBMN cells in vitro resulted in increased (P < 0.01) proliferation (at a dose of 100 ng/ml). Higher doses of oGH (2 μg/ml) also increased PBMN cell proliferation. When PBMN cells were previously stimulated with IL-2, the dose of 100 ng/ml oGH was no longer able to stimulate proliferation. IGF-1 inhibited (P < 0.04) resting PBMN cell proliferation at 100 ng/ml but had no effect on IL-2-activated PBMN cells. Other hormones such as PRL caused a stimulation of PBMN cell proliferation (P < 0.01) at 100 ng/ml, whereas dexamethasone (dex) inhibited PBMN cell proliferation at doses as low as 63 ng/ml. These studies show that GH, PRL, IGF-1, and glucocorticoids are effective in modulating the proliferation of PBMN cells from sheep and therefore suggest that a modulation of immune system function in vitro by these hormones is consistent with a purpose in vivo.

Thirteen Targhee rams selected for rate and efficiency of gain for 4 yr (1.5 generations) were compared with 10 rams from a Targhee line with no selection for over 20 yr to determine if selection for these traits would be associated with changes in the secretion of growth hormone (GH), thyrotropin (TSH) and(or) prolactin (PRL). Selected rams exhibited greater birth weight, average daily gain (ADG) and feed consumed/day during a 6-wk individual feeding regimen, and exhibited greater overall ADG during a 16-wk feeding trial as compared with the unselected rams. Temporal blood plasma samples were collected at 15-min intervals for 8 h from each of the 23 rams for hormone analysis. Selected rams exhibited greater overall mean GH (6.1 +/- .4 vs 4.6 +/- .5 ng/ml), overall mean TSH (8.6 +/- 1.2 vs 6.2 +/- .7 ng/ml) and baseline mean TSH (8.0 +/- 1.1 vs 5.6 +/- .5 ng/ml) than the unselected rams. Although the adjusted GH spike amplitude value was higher in the selected line (12.1 +/- 3.0 vs 7.4 +/- .8 ng/ml), this difference was not significant. No differences were observed with any of the variables of PRL secretion. In addition, there were no significant correlations between any of the hormone variables and any of the feed or gain data. These data support the hypothesis that Targhee rams selected for rate and efficiency of gain exhibit higher plasma levels of GH and TSH than unselected rams of the same breed.

Concentrations of luteinizing hormone (LH) and prolactin (Prl) in the serum of anestrous and cycling ewes were compared. The concentration of LH in serum and the frequency of episodic releases of LH were lower in anestrous than in cycling ewes. Concentrations of LH in serum rose as rapidly after ovariectomy of anestrous ewes as after ovariectomy of cycling ewes. Prl levels were higher during anestrus than at any stage of the estrous cycle; however, high Prl levels were not necessarily associated either with low LH levels or the absence of episodic release of LH. These data suggest: (1) that anestrus is not due to a reduction in the intrinsic ability of the hypothalamo-hypophyseal system to secrete LH, and (2) that high Prl levels may be a symptom rather than a cause of seasonal anestrus.

A series of experiments were conducted in ewes and whether (castrate male) lambs to evaluate the influence of prostaglandins on secretion of anabolic hormones and to determine if repeated injections of prostaglandin (PG) F2alpha would chronically influence the secretion of these hormones and perhaps growth rate as well. A single intravenous injection of PGA1 and PGB1 (100 microgram/kg) exerted no significant (P greater than .10) influence on plasma concentrations of prolactin (PRL), growth hormone (GH) or thyrotropin (TSH) in ewes. PGA1, but not PGB1, stimulated an increase in the plasma concentration of insulin. Infusion of PGF2alpha for 5.5 hr into ewes resulted in increased (P less than .05) plasma concentrations of both GH and ARL while TSH and insulin were not significantly influenced. Prostaglandin F2alpha, when injected subcutaneously into wether lambs (10 mg twice weekly) stimulated (P less than .05) plasma GH concentrations after the first injection, but not after 3 weeks of treatment. Changes in plasma PRL or TSH were not observed consistently in the lambs treated chronically with PGF2alpha or TRH. Prostaglandin F2alpha, in the present studies, and PGE1 in previously reported studies (1-3), has been demonstrated to be stimulatory to the secretion of PRL and GH. In contrast, PGA1 and PGB1, which lack an 11-hydroxyl group, failed to influence the secretion of either PRL or GH. It would, therefore, appear that the 11-hydroxyl group is a structural requirement for prostaglandins to influence the secretion of these two hormones in sheep. Treatment with thyrotropin releasing hormone (TRH), alone or in combination with PGF 2alpha, significantly (P less than .05) increased growth rate (average daily gains) while PGF2alpha did not, despite the fact that both compounds exerted similar effects on plasma GH.

Plasma levels of thyrotropin (TSH), prolactin (Prl), growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) were measured in response to continuous 24-h infusion of synthetic thyrotropin-releasing hormone (TRH) in normal and surgically thyroidectomized (THYX) calves in a series of 2 experiments. In the 1st experiment, the low dose of TRH (0.077 microgram/min) had no effect on any hormone levels measured. Plasma TSH concentration increased significantly (p less than 0.05) in response to TRH infusion (0.77 microgram/min) in both experiments, but plasma TSH levels plateaued and then declined in both cases despite continued TRH infusion and irrespective of the presence or absence of a thyroid gland. A similar pattern of secretion, though less markedly decreased over time, was observed for plasma Prl in both experiments. The higher dose (0.77 microgram/min) of TRH had no effect on plasma GH concentration in the 1st infusion, but did result in a significant (p less than 0.05) increase in overall mean concentration of GH in both normal and THYX calves in the 2nd experiment. Removal of the thyroid gland, thus removing the source of increasing T4 and T3 levels seen in normal calves infused with TRH, failed to alter the secretory patterns of TSH and Prl. These data suggest that feedback inhibition by increasing plasma thyroid hormone concentrations was not responsible for the failure of TSH and, to a lesser extent, Prl to maintain chronically elevated plasma levels in response to continuous 24-h TRH infusion. It is suggested that a depletion of pituitary TSH and Prl stores readily secretable in response to a constant dosage level of TRH may be responsible for the secretory patterns observed.

We examined constancy of release of purified ovine growth hormone from an implant containing soybean oil and bees-wax. Implants contained an amount of growth hormone that was sufficient to increase concentrations in blood plasma by 20 and 40ng/ml and to maintain those concentrations over 1 wk. Growth hormone in plasma increased to approximately 65ng/ml in lambs receiving low dose implants the 1st day after implantation, returned to 31ng/ml on day 2, and remained near this concentration for the remainder of the week. Pulse release of growth hormone was not similar in the high dose lambs where growth hormone concentration in plasma averaged 45ng/ml 1 day after implantation, then gradually increased to 60ng/ml on day 6. Unimplanted control lambs had mean growth hormone concentrations of 2.9 to 3.9ng/ml throughout the 6-day observation. This approach should interest investigators studying the chronic influence of purified or synthetic growth hormone on dairy cows, beef steers, or lambs.

The influence of anabolic steroids on growth hormone (GH) secretion in ruminants remains unclear, perhaps because of the dynamic nature of GH secretion. In the present study, blood samples were obtained at 15-min intervals for 12 h from intact ram lambs, ram lambs castrated postpubertally, and castrated ram lambs treated with either testosterone propionate (TP) or diethylstilbestrol (DES). Intact rams exhibited GH secretory episodes of greater (P less than 0.01) amplitude than did castrated lambs. Similarly, mean base-line and mean overall GH concentrations were higher (P less than 0.01) in rams than in castrates. Treatment of castrates with either TP or DES resulted in increased base-line (P less than 0.05) and overall (P less than 0.05) GH concentrations compared to untreated castrates. Although amplitude of GH spikes was larger in TP and DES groups, this difference was not statistically significant (P greater than 0.05). Because numerous studies have demonstrated that intact rams and castrates treated with TP or DES grow faster than untreated castrates, the data in the present study support the hypothesis that the anabolic action of androgens and estrogens is due, at least in part, to their influence on GH secretion.