H.A. Tucker

Neuroregulation of growth hormone secretion in domestic animals

Growth hormone (GH) is essential for postnatal somatic growth, maintenance of lean tissue at maturity in domestic animals and milk production in cows. This review focuses on neuroregulation of GH secretion in domestic animals. Two hormones principally regulate the secretion of GH: growth hormone-releasing hormone (GHRH) stimulates, while somatostatin (SS) inhibits the secretion of GH. A long-standing hypothesis proposes that alternate secretion of GHRH and SS regulate episodic secretion of GH. However, measurement of GHRH and SS in hypophysial-portal blood of unanesthetized sheep and swine shows that episodic secretion of GHRH and SS do not account for all episodes of GH secreted. Furthermore, the activity of GHRH and SS neurons decreases after steers have eaten a meal offered for a 2-h period each day (meal-feeding) and this corresponds with reduced secretion of GH. Together, these data suggest that other factors also regulate the secretion of GH. Several neurotransmitters have been implicated in this regard. Thyrotropin-releasing hormone, serotonin and gamma-aminobutyric acid stimulate the secretion of GH at somatotropes. Growth hormone releasing peptide-6 overcomes feeding-induced refractoriness of somatotropes to GHRH and stimulates the secretion of GHRH. Norepinephrine reduces the activity of SS neurons and stimulates the secretion of GHRH via alpha(2)-adrenergic receptors. N-methyl-D,L-aspartate and leptin stimulate the secretion of GHRH, while neuropeptide Y stimulates the secretion of GHRH and SS. Activation of muscarinic receptors decreases the secretion of SS. Dopamine stimulates the secretion of SS via D1 receptors and inhibits the secretion of GH from somatotropes via D2 receptors. Thus, many neuroendocrine factors regulate the secretion of GH in livestock via altering secretion of GHRH and/or SS, communicating between GHRH and SS neurons, or acting independently at somatotropes to coordinate the secretion of GH.

Prolactin and Growth Hormone Circadian Periodicity in Lactating Cows

Summary Prolactin and growth hormone in serum of 10 lactating cows was measured by radioimmunoassay at hourly intervals on 4 days. Prolactin in lactating cows was released in erratic pulses throughout the day. Serum prolactin concentration followed a 24-hr periodicity (p < .01), with the highest value occurring at 4:00 p.m. (58 ng/ml) and lowest values being recorded between 4 and 10 a.m. (28 ng/ml). However, circadian changes accounted for only 8% of the total variation in prolactin values, differences within cows accounted for 45% and differences among cows accounted for 47%. Serum growth hormone concentration was more stable than prolactin and did not exhibit circadian periodicity.

Plasma prolactin, growth hormone, luteinizing hormone and glucocorticoids after prostaglandin F2alpha in heifers.

Summary Blood plasma PRL, GH and glucocorticoids in heifers increased severalfold within 5-15 min after im injections of 15, 30, or 60 mg PGF2α or after a single 5 mg iv injection of PGF2α. Plasma LH increased at least twofold over basal estimates but not until 1.5-6 hr after im PGF2α. Constant iv infusion of PGF2α at the rate of 0.5 mg/min for 30 min produced greater plasma concentrations of PRL, GH, glucocorticoids and LH than those found after im injections. Plasma glucose increased 59-67% above pretreatment values between 30 and 60 min after iv administration of PGF2α. Plasma insulin increased more than twofold over basal estimates at 45 min after PGF2α administration, but these increases only approached significance (P ≃ 0.10). Free fatty acids did not change significantly (P > 0.05) after PGF2α administration. While exogenous PGF2α administration causes marked increases in several plasma hormones and glucose, the mechanism of action is unclear.

5-Hydroxytryptaminergic Receptor-Stimulated Growth Hormone Secretion Occurs Independently of Changes in Peripheral Somatostatin Concentration

Abstract Effects of activation or blockade of 5-hydroxytryptaminergic receptors on concentrations of growth hormone and somatostatin in serum were studied in Holstein steers (mean ± SEM: 159 ± 8 days of age; 160 ± 9 kg of body wt). A pelleted diet was available ad libitum between 1000 and 1200 hr each day. Blood was sampled from a cannula in a jugular vein. Peak concentration of growth hormone in serum within 1 hr before feeding (12.8 ± 3.8 ng/ml) was greater than peak concentration within 1 hr after removal of feed (3.3 ± 1.0 ng/ml). In contrast, concentration of somatostatin in plasma did not change from 1 hr before feeding through 1 hr after removal of feed (47.3 to 43.0 ± 4.5 pg/ml). Relative to saline-injected controls, activation of 5-hydroxytryptaminergic receptors with quipazine (0.05, 0.1, and 0.2 mg/kg body wt, iv) increased the area under growth hormone response curves 5.5- to 25-fold before and after feeding. In another experiment, injection of 0.1 mg of quipazine/kg body wt at 1300 hr increased the concentration of growth hormone in serum 7.8-fold compared with controls, but had no effect on concentration of somatostatin in plasma. Relative to water-injected controls, blockade of 5-hydroxytryptaminergic receptors with cyproheptadine (0.2 mg/kg body wt, sc) decreased the area under growth hormone response curves for at least 110 min before feeding (71%) and after removal of feed (69%). The data support the hypothesis that 5-hydroxytryptaminergic receptors are involved in stimulation of pulsatile growth hormone secretion in meal-fed cattle. Lack of a change in concentration of somatostatin in plasma with respect to time of meal-feeding or after injection of the 5-hydroxytryptaminergic-receptor agonist quipazine suggests that 5-hydroxytryptaminergic receptor-stimulated growth hormone secretion is likely mediated within the central nervous system, rather than by meal-induced changes in peripheral secretion of somatostatin.

Clearance and secretion rates of prolactin in dairy cattle in various physiological states.

Summary Basal clearance rates (CR; ml/min/kg body wt) and secretion rates (SR; μg/hr/kg body wt) of prolactin (PRL) were calculated for Holstein cows. Among late lactating, pregnant cows (n = 8) tested in December, estimates of basal CR and SR were not different (P > 0.05) during infusion of either 4 or 8 mg PRL/cow/hr for 4 hr. In a second experiment, basal CR estimates were similar (P > 0.05) in four nonlactating and four early lactating cows but basal SR was 35% greater (P ~ 0.1) in early lactating than in nonlactating cows tested in April. In a third experiment designed to avoid possible seasonal effects, basal CR estimates of PRL were 75 and 25% greater and basal SR estimates 140 and 40% greater (P < 0.05) in early lactating and late lactating cows than in nonlactating cows, respectively. Differences in basal CR and SR of PRL among all lactating cows were correlated with mean daily milk production (r = 0.36; P < 0.05 and r = 0.52; P < 0.005, respectively) during the week prior to each experiment. We conclude that increased basal CR and SR of PRL are associated with increased milk yields in dairy cows.

Regulation of growth hormone-releasing hormone and somatostatin from perifused, bovine hypothalamic slices. II. Dopamine receptor regulation

An in vitro perifusion system for bovine hypothalamic tissue was utilized to examine the role of D1 and D2 dopamine receptors in the regulation of somatostatin (SRIF) and growth hormone-releasing hormone (GHRH) release. Up to three sagittal slices (600 microns) of bovine hypothalamus, immediately parallel to the midline, were cut in an oxygenated balanced salt solution at 4 degrees C, placed in 5 cc syringes, and perifused at 37 degrees C with oxygenated minimum essential medium-alpha at a flow rate of 0.15 ml/min. Five experiments were conducted, and medium effluent was collected every 20 min before (two samples), during (one or three samples), and after (six samples) treatment. Areas under SRIF and GHRH response curves (AUC), adjusted by covariance for pretreatment values, were calculated from samples collected during the treatment/post-treatment period. Activation of D1 receptor with 10(-8) M and 10(-6) M SKF 38393 increased AUC for SRIF from 5.6 (control) to 420 and 500 +/- 57.8 ng.ml-1 min, but 10(-10) M SKF 38393 was ineffective. Relative to controls, release of GHRH was decreased 50% in the 10(-6) M SKF 38393 group. Blockade of D1 receptors with SCH 23390 had no effect on basal release of either SRIF or GHRH, but prevented SKF 38393-induced release of SRIF and SKF 38393-induced suppression of GHRH. In contrast, quinelorane, a D2 receptor agonist, and haloperidol, which blocks D2 receptors, did not affect release of SRIF or GHRH. We concluded that activation of D1 dopamine receptors, but not D2 dopamine receptors, stimulates release of SRIF and inhibits release of GHRH from the bovine hypothalamus.

Intensive nursing and lactational performance during extended lactation.

Summary Intensive nursing (6 pups/6 intact abdominal-inguinal mammary glands, and replacing all 16-day-old litters every 4 days with 12-day-old foster litters) failed to prevent significant declines in mammary DNA, RNA, and litter weight gains between days 20 and 36 of lactation. But no comparable changes in lactic acid content of mammary glands were observed. Intense nursing maintained pituitary prolactin during extended lactation but ACTH decreased 67.6%. Thus, ACTH may be rate limiting to milk synthesis during extended lactation.

α2-Adrenergic Receptor-Mediated Regulation of Growth Hormone Secretion in Meal-Fed Holstein Steers

Abstract Effects of activation or blockade of α2-adrenergic receptors on serum growth hormone concentrations were studied in Holstein steers (115 ± 4 days of age; 112 ± 4 kg body wt). A pelleted diet was available ad libitum for 2 hr each day. Serum growth hormone concentrations were greater for 80 min immediately before feeding compared with 80 min immediately after removal of feed. Relative to saline-injected controls, activation of α2-adrenergic receptors with clonidine (2 μg/kg body wt iv) before feeding rapidly increased serum growth hormone concentrations, but clonidine had no effect when administered after feeding. Compared with vehicle-injected controls, blockade of α2-adrenergic receptors with either idazoxan (20 mg/kg body wt sc) or yohimbine (5 mg/kg body wt sc) decreased serum growth hormone concentrations before as well as after feeding. Feeding abolished the stimulatory α2-adrenergic receptor-mediated increase in growth hormone secretion. Our data support the hypothesis that α2-adrenergic receptor stimulation is an essential event mediating pulsatility of growth hormone secretion before feeding and is required to maintain basal concentrations after feeding.

Temperature effects on serum prolactin concentrations and activity of dopaminergic neurons in the infundibulum/pituitary stalk of calves

Abstract The effects of ambient temperature on serum concentrations of prolactin and neurochemical estimates of activity of dopaminergic neurons projecting to the infundib-ulum/pituitary stalk were investigated in Holstein bull calves. Accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the infundibulum/pituitary stalk after intravenous injection of a decarboxylase inhibitor was used to estimate activity of these dopaminergic neurons. Increasing ambient temperature from 21 to 33°C for 22 hr increased serum concentrations of prolactin and decreased activity of the dopaminergic neurons. Conversely, reducing ambient temperature from 22°C to 11°C decreased serum concentrations of prolactin and increased activity of these dopaminergic neruons. It is suggested that alterations in activity of dopaminergic neurons terminating in the infundibulum/pituitary stalk of bull calves may mediate acute temperature-induced changes in secretion of prolactin.

Adrenal Function During Prolonged Lactation

Summary Adrenal corticosterone content and concentration decreased linearly from days 16 to 32 of lactation. Peripheral plasma concentrations of corticosterone in lactating rats were higher than the resting levels measured in virgin rats. However, corticosterone concentrations in plasma did not change significantly between days 16 and 32 of lactation. Rats killed at day 32 of lactation had a greater plasma corticoid binding globulin (CBG) activity than rats killed at days 16 and 24. Adrenal corticosterone content was correlated significantly with mammary gland RNA, DNA, and litter weight gain. The data support the concept that adrenal secretions may be rate limiting to milk synthesis during prolonged lactation.