Exogenous GH-releasing Factor Research Articles

Effect of exogenous growth‐hormone‐releasing factor on blood metabolites and minerals in late maturing buffalo heifers (Bubalus bubalis)

Previous studies have suggested that growth-hormone-releasing factor (GRF) enhanced growth and advanced puberty onset along with hormonal changes in buffalo heifers (Bubalus bubalis). However, it is not known to what extent exogenous GRF could influence blood metabolites and minerals to bring about puberty in buffalo heifers. Therefore, we planned to investigate the effect of exogenous bovine GRF (bGRF) on blood metabolites and minerals in buffalo heifers during a 3-month pre-treatment period, 9-month treatment period and 1-month post-treatment period. Six buffalo heifers were treated intravenously with bGRF (10 mug per 100 kg body weight) at 15-day interval for 9 months. Another six buffalo heifers of weight- and age-matched received requisite amount of vehicle (0.9% NaCl solution) during the same period. Exogenous bGRF enhanced (p < 0.01) plasma non-esterified fatty acids (NEFA) concentrations in treatment group when compared with control group during the treatment and post-treatment period, while plasma alpha-amino nitrogen (AAN) concentrations showed a decreasing trend (p < 0.05) in the treatment group when compared with the control group during the treatment and post-treatment periods. The plasma inorganic phosphorus (Pi) was found to be higher (p < 0.05) in the treatment group animals in comparison with the levels recorded in the control group animals during the treatment as well as post-treatment periods. However, there was no change (p > 0.05) in plasma glucose and calcium concentrations between the two groups. Plasma NEFA was found to be positively correlated with plasma growth hormone (GH); however, it was only significant for the treatment group (r = + 0.76; p < 0.05). Plasma AAN in the treatment group exhibited negative correlation with plasma GH (r = 0.72; p < 0.05), while plasma AAN and GH were recorded to be positively correlated in the control group (r = 0.47; p < 0.05). The present findings suggest that exogenous bGRF induces GH release that increases plasma NEFA and Pi and decreases AAN concentrations, which probably help to reach a certain physiological state that initiates events necessary for bringing about puberty in buffalo heifers.

Effects of long-term growth hormone-releasing factor administration on plasma growth hormone, luteinizing hormone and progesterone profiles in growing female buffaloes (Bubalus bubalis).

To investigate the effects of long-term growth hormone-releasing factor (GRF) administration on plasma growth hormone (GH), LH and progesterone and body weight gain in growing buffalo calves, 12 female Murrah buffaloes within the age group of 6-8 months of age were divided into two groups (treatment and control groups) of six each in such a way so that average body weights between the groups did not differ (p > 0.05). Control buffaloes were not given any hormonal treatment and treatment group buffaloes were treated with synthetic bovine GRF [bGRF (1-44)-NH(2)] at the rate of 10 microg/100 kg body weight intravenously at an interval of 15 days from week 6 (5-week pre-treatment period) till 18 injections were completed (week 6-42 treatment period) and thereafter, effect of exogenous GRF were observed for 10-week post-treatment period. Jugular blood samples were drawn twice a week at 3-4-day intervals for plasma GH, LH and progesterone quantification. Body weight of all animals was recorded twice a week. During pre-treatment period, mean plasma GH, LH and progesterone did not differ (p > 0.05) between the groups. But during treatment as well as post-treatment period, mean plasma GH levels were found to be significantly (p < 0.01) higher in treatment than control group of buffaloes. Administration of GRF for longer term sustained a higher level of plasma GH even after cessation of treatment. GRF-treated buffaloes attained higher (p < 0.01) body weight than the controls. Repeated GRF administration for long-term significantly (p < 0.01) increased plasma LH and progesterone. In conclusion, repeated long-term exogenous GRF administration induces and even enhances GH release without any sign of refractoriness. GRF may, therefore, be used to induce daily GH release without loss of responsiveness over an extended period of time in young growing female buffaloes and it may assist these animals to grow faster.

Effects of GRF in early gestation on foetal development in Large White and Genex-Meishan gilts

The effects of growth hormone-releasing factor (GRF), given in early gestation, on reproductive traits, foetal development and pre-weaning growth of piglets from two breeds were studied. Large White (LW, n = 26) and Genex-Meishan (GM, containing 50% Meishan genes, n = 37) pregnant gilts were divided in two groups: (1) saline injections (n = 33) and, (2) injections of 6.66 µg kg-1 of a GRF analogue (n = 30), given thrice daily from days 18 to 33 of gestation. Jugular blood samples were collected on days 17, 34 and 109 of gestation and were assayed for various hormones and metabolites. Thirty-six gilts were slaughtered on day 110 of gestation and uterine, foetal and placental measurements were obtained. The other 27 gilts farrowed. There was a day × treatment interaction (P &lt; 0.001) for glucose, insulin, free fatty acids (FFA) and insulin-like growth factor I (IGF-I), with values being greater on day 34 in gilts receiving GRF. The increase in insulin concentration was greater in LW- than in GM-treated gilts (P = 0.02). Exogenous GRF increased foetal weight in LW litters only (1.13 ± 0.04 vs. 1.05 ± 0.03 kg; P = 0.04) whereas fat content of carcasses tended to be lower only in foetuses of treated GM gilts (5.3 ± 0.2 vs. 5.8 ± 0.2%; P = 0.1). Weight of the longissimus muscle and its fibre number were not influenced by GRF. Furthermore, growth of piglets to 28 d was not affected by GRF treatment (P &gt; 0.1). In conclusion, GRF given in early gestation seems to have different effects in LW and GM litters, yet it does not alter pre-weaning growth rate. Key words: Molybdenum, molybdenosis, copper, mine tailings, reclamation, animal health

Maternal undernutrition alters triiodothyronine concentrations and pituitary response to GnRH in fetal sheep.

The aims of this study were to determine which hormones may have a role in the expression of maternal undernutrition effects on reproductive function, in both the developing fetus and the adult offspring. This was undertaken by measuring the effects of long-term maternal undernutrition on metabolic hormone profiles and pituitary responses to single doses of GnRH and GH-releasing factor (GRF) in fetal sheep. From mating, groups of ewes were fed rations providing either 100% (HIGH) or 50% (LOW) of estimated metabolisable energy requirements for pregnancy throughout the experiment until slaughter at approximately 119 days of gestation. Fetal and maternal blood samples were collected from 113 until 119 days of gestation, via carotid and jugular catheters respectively, and assayed for insulin, IGF-I, GH, thyroxine and triiodothyronine (T(3)). Undernutrition had no effects on fetal weight, fetal gonad weight of either sex, fetal insulin or IGF-I concentrations. Male LOW fetuses exhibited a significantly attenuated response (P<0.05) to a bolus challenge of GnRH compared with HIGH fetuses. Basal fetal GH concentrations and the response to exogenous GRF were similar in both treatment groups, although LOW fetuses exhibited more secretory episodes (P<0.01). Mean T(3) concentrations were significantly lower in both the maternal (P<0.01) and fetal (P<0.05) plasma of LOW animals compared with HIGH animals. It is concluded that pituitary function was altered in fetal males and could influence male reproductive development. On the other hand, in female sheep, fetal gonadal abnormalities and reductions in reproductive capacity in adult life which are associated with fetal undernutrition are unlikely to be attributable to altered pituitary function. Additionally, these studies raise the possibility that thyroid hormones may have a role in the expression of maternal undernutrition effects on fetal development.

Lead attenuation of episodic growth hormone secretion in male rats.

The purpose of this study was to characterize the effects of chronic lead exposure on growth hormone and insulin-like growth factor-1 status in growing male rats. Pituitary growth hormone content, episodic growth hormone release, plasma insulin-like growth factor-1 levels, and growth hormone response to exogenous growth hormone-releasing factor were quantified in young rats given lead nitrate. Twenty male Sprague-Dawley weanling rats were given lead nitrate (1000 ppm lead) in drinking water for a period of 6 weeks. Lead treatment significantly reduced body weight gain. Pituitary growth hormone content was not altered by lead treatment. Mean plasma growth hormone levels were reduced 44.6% by lead treatment (46.41 +/- 6.2 ng/ml; p = .003) as compared to controls (83.82 +/- 10 ng/ml). Lead treatment reduced mean growth hormone peak amplitude by 37.5%, mean nadir concentration by 60%, and growth hormone peak area by 35%. These findings are consistent with decreased hypothalamic growth hormone-releasing factor secretion or reduced somatotrope responsiveness. Exogenous growth hormone-releasing factor increased plasma growth hormone in lead-treated and control rats. However, this response was blunted by the lead treatment (lead treated: 485.6 +/- 57.8 vs. controls: 870.2 +/- 127 ng/ml; p = .03). Plasma insulin-like growth factor-1 concentration was not significantly affected by lead treatment. These results demonstrate that lead intoxication attenuates growth hormone release without abolishing the hypothalamic endocrine mechanisms driving growth hormone pulsatility. This suggests that lead acts at the level of the pituitary somatotroph rather than at the level of the hypothalamus.

Mammary gland development of sows injected with growth hormone-releasing factor during gestation and(or) lactation

Twenty-four gilts received s.c. injections of saline or growth hormone-releasing factor (GRF) in late gestation and(or) lactation. Sows were sacrificed on day 30 of lactation and functional mammary glands were excised for chemical analyses. Weight of parenchymal (P = 0.004) and extra-parenchymal tissues (P = 0.002) were decreased with GRF injections during lactation. Parenchymal mass per milligram of DNA also decreased (P = 0.025) with GRF in lactation while parenchymal DNA concentration increased (P = 0.03). Exogenous GRF given to sows during lactation therefore decreased total parenchymal mass, increased cell density and decreased mammary cell size. Key words: Sow, mammary gland, growth hormone-releasing factor

In vivo evidence of a positive role for somatostatin to optimize pulsatile growth hormone secretion.

Despite convincing evidence that somatostatin (SRIF) and growth hormone (GH)-releasing factor (GRF) individually play crucial roles in GH regulation, the nature of the interplay between these two hypothalamic hormones is far from clear. In the present study, we used the long-acting SRIF analogue, octreotide, as a probe in both the normal and mutant dwarf (dw) rat 1) to further elucidate the temporal nature of the SRIF-GRF interaction in vivo and 2) to define possible mechanisms of action of SRIF in generating pulsatile GH secretion. Normal free-moving adult male rats pretreated with octreotide (25 and 50 micrograms iv) and subsequently challenged with GRF (1 micrograms iv) exhibited a markedly blunted GH response to exogenous GRF 1 h after treatment. In contrast, preexposure to octreotide for 3 h produced a two- to threefold augmentation in GH responsiveness to GRF. Compared with normal saline-pretreated controls, 3-h pretreatment with octreotide produced a 14- to 16-fold augmentation in the postinhibitory rebound release of GH after the coadministration of native SRIF-14 and GRF (P < 0.001). In dw rats, which show a selective reduction in GH synthesis and storage, 3-h preexposure to octreotide failed to significantly alter GRF-induced GH release. These results demonstrate that, in the normal male rat, a 3-h period of exposure to the SRIF analogue octreotide is sufficient to enhance GH responsiveness to GRF. Our findings suggest that this effect is due to a SRIF-mediated buildup of pituitary GH stores in a readily releasable poo.(ABSTRACT TRUNCATED AT 250 WORDS)

Immuno-enhancement and -inhibition of GH-releasing factor by site-directed anti peptide antibodies in vivo and in vitro.

It is now well established that specific antibodies and binding proteins can potentiate rather than inhibit hormone activity. In order to investigate this phenomenon further, the current study was undertaken using a hormone with a characterised structure, in terms of receptor binding, and for which activity has already been manipulated in specific ways (prolongation of half-life, increased receptor affinity) using synthetic hormone analogues. GH-releasing factor (GRF) is a 40 or 44 residue peptide and is, together with somatostatin, responsible for the regulation of GH secretion. The effects of site-directed anti peptide antibodies were determined on the activity of GRF in vivo and in vitro as GH release. The peptide regions of GRF were: 1-14 (part of putative receptor-binding region) and 31-44 and 35-44 (sites thought to be distant from the receptor-binding region). Five sheep were administered GRF (1 microgram/kg), anti peptide immunoglobulin (Ig; a calculated tenfold excess binding to GRF dose), or GRF together with anti peptide Ig (preincubated for 1 h). GRF induced a significant increase in plasma GH concentration over the next 240 min, this was abolished when GRF was administered with anti 1-14 Ig (P < 0.05) and augmented (P < 0.05) when GRF was administered with anti 35-44 Ig; anti 31-44 had no effect on GRF activity. Anti 35-44 Ig alone induced an increase in GH secretion which was equivalent to that for GRF alone, implying that the antibody had interacted and potentiated with endogenous GRF. The Ig effects on exogenous GRF activity were confirmed for GH release in vitro using primary cultures of sheep pituitary cells, except that anti 31-44 Ig also augmented GH release (P < 0.05) when co-administered with GRF. (ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone response after administration of growth hormone-releasing factor to proven dairy sires

To estimate the potential of GH response to administration of growth hormone (GH)-releasing factor (GRF) as a predictor of genetic merit, two experiments, utilizing proven AI dairy sires of differing genetic merit for milk production, were conducted. In a first experiment, bulls of superior genetic merit [S; n=4; genetic merit for economic value of product (MFP$)=$227] or inferior genetic merit (I; n=4; MFPS=$94) were administered, three dosages of GRF (0, 5.5 and 11 μg GRF · 100 kg BW −1). Each bull received one dosage of Ro23-7863, an hGRF (1–29) analog, on each of three consecutive days. Area under the GH response curve (AUC) from S bulls following 5.5 or 11 μg GRF were greater (P<0.01) than AUC from I bulls. In a second experiment, a single dosage of GRF (4 μg GRF · 100 kg BW −1) was administered to sires of superior (S; n=8; MFPS=$204), average (A; n=8; MFP$=$149) or inferior (I; n=8; MFPS=$74) genetic merit. There was no effect (P>0.05) of genetic group on preinjection AUC, however, AUCs following GRF were greater (P < 0.01) from S and A sires compared with I sires (1925 and 1676 vs. 549 ng min ml −1, respectively). Therefore, GH response to exogenous GRF administration may be a useful tool in identifying dairy bulls with superior transmitting ability for milk production traits.

Carcass composition and resistance to fasting in neonatal piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor injections during gestation.

Thirty-eight gestating sows were either immunized against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF). Treatment effects on carcass composition and resistance of newborn piglets to a 60-hour fast were investigated. Protein content of carcasses at birth was increased in piglets of sows receiving GRF or immunized against SRIF, however, when sows received both treatments there was a reduction in carcass protein content (p = 0.01). Other carcass components were unaltered by treatments, and none of the treatments affected metabolic or endocrine profiles of piglets at birth. Concentrations of GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased linearly with duration of fast, whereas glucose values decreased. Resistance to fasting was unaltered in piglets from any treatment thereby suggesting that exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to improve survival of newborn piglets.

Antagonism of central growth hormone-releasing factor activity selectively attenuates dark-onset feeding in rats

Exogenous growth hormone-releasing factor (GRF) has been shown to activate feeding by central mechanisms involving the suprachiasmatic nucleus/medial preoptic area (SCN/MPOA). Until now, however, the role played by endogenous GRF in the SCN/MPOA in naturally occurring eating has remained unknown. To investigate this, the effects of SCN/MPOA injections of GRF antiserum (AS-GRF) on feeding in rats were studied. In light of SCN involvement in the control of circadian rhythms, AS-GRF was tested during the light and dark phases of the photoperiod. Results indicated that AS-GRF significantly attenuated dark-onset feeding but had no effect on feeding during the mid-dark, mid-light, or light-onset periods. These results suggest that endogenous GRF does play a role in naturally occurring feeding and that it may be involved in the circadian organization of feeding.

Effects of infusions of various doses of bovine growth hormone-releasing factor on blood hormones and metabolites in lactating Holstein cows

In two experiments, the effects of i.v. infusions of various doses of bovine GH-releasing factor (GRF) on blood hormones and metabolites in lactating Holstein cows were determined. In experiment 1, cows were infused with GRF (0, 3.125, 6.25, 12.5, 25.0 or 50.0 mg/cow per 24 h) for 24 h. Blood was sampled at -1, 5, 11, 15 and 23 h relative to the start of the infusion. The serum concentration of somatomedin C (SM-C) before infusion was 303 +/- 8 (S.E.M.) micrograms/l. Doses of GRF of between 3.125 and 50.0 mg were equipotent in stimulating (P less than 0.05) SM-C by 1.5- to 2.5-fold. GRF-induced increases in SM-C occurred by 11 h from the start of the infusion. In experiment 2, primiparous cows were infused with GRF (0, 1 or 3 mg/24 h) for 20 days. Blood was sampled for 12 h on days 1, 10 and 19. The 1 mg dose of GRF increased (P less than 0.05) blood concentrations of SM-C (on days 10 and 19) and glucose (on day 19), but did not affect blood concentrations of prolactin, insulin, cortisol, tri-iodothyronine (T3), thyroxine (T4), non-esterified fatty acids (NEFA) or glucose. The 3 mg dose of GRF increased (P less than 0.05) blood concentrations of SM-C (on days 10 and 19), T3 (on days 10 and 19), insulin (on day 19), NEFA (on days 1, 10 and 19) and glucose (on day 19), but did not affect blood concentrations of prolactin, cortisol or T4. We conclude that these data are consistent with the hypothesis that the galactopoietic effect of exogenous GRF in dairy cattle is mediated by increased secretion of GH.

Effects of Active Immunization Against Somatostatin on Serum Growth Hormone Concentration in Growing Pigs: Influence of Fasting and Repetitive Somatocrinin Injections*

Three experiments were conducted with growing pigs actively immunized against a protein-conjugated somatostatin (SRIF) in Freund's adjuvant. In the first experiment, blood from 24-week-old pigs (seven immunized and eight control) was sampled at 20-min intervals for 6 h to evaluate basal GH concentrations. The animals were then injected iv with porcine GH-releasing factor (GRF)-(1-29)NH2 (10 micrograms/kg). Before GRF stimulation, immunized animals had higher (P less than 0.05) baseline mean GH levels (2.6 vs. 1.4 ng/ml) and area under the GH curve (AUC; 1632 vs. 779 ng/min.ml); they also had higher AUC after GRF administration (4268 vs. 1972 ng/min.ml). In a second experiment eight immunized and eight control pigs were injected iv four times at 90-min intervals with porcine GRF (10 micrograms/kg). Control pigs responding to the first injection did not respond to the second and third, and those responding to the second did not respond to the first, third, and fourth, indicating a decreased responsiveness that was longer than 3 h post-GRF response in control pigs. SRIF-immunized pigs had a more consistent GH response to the GRF injections. Overall, a reduced response was observed after the second and the fourth injections in immunized pigs, although five and six of eight animals had a GH peak response higher than 10 ng/ml during these periods. In a third experiment, effects of fasting, GRF, and SRIF immunization were studied. Immunization and fasting had their own positive effects on serum GH levels. Immunization increased baseline mean GH levels (5.0 vs. 2.2 ng/ml) and total AUC before (2318 vs. 1073 ng/min.ml) and after (1886 vs. 910 ng/min.ml) iv GRF stimulation (10 micrograms/kg) compared to controls. Fasting increased the mean baseline GH level (4.5 vs. 2.6 ng/ml), and it increased AUC before exogenous GRF stimulation (2009 vs. 1392 ng/min.ml). In conclusion, SRIF in pigs seems to be a potent GH-governing factor, since, when inhibited, baseline mean GH levels increase, and a consistent response to GRF is observed. Fasting could increase GH concentrations by different ways: decreasing SRIF release and increasing GRF release or modifying the sensitivity of the somatotrophs to both factors.

Effects of growth hormone-releasing factor and somatostatin on growth hormone secretion in hypophysial stalk-transected beef calves.

The effects of growth hormone-releasing factor (GHRF) on growth hormone (GH) secretion were studied in beef calves after hypophysial stalk transection (HST). Peripheral GH concentration during surgery was elevated for 60 min after the initiation of anesthesia to 15 ng/ml, which was greater than plasma levels after HST and during the recovery period (0-30 hr mean, 3 ng/ml; P less than 0.05). Episodic GH secretion normally seen in sham-operated controls (SOC) was abolished after HST. Before HST, calves responded to 80% of the GHRF challenges, whereas after HST calves responded to every challenge of GHRF with an increase in plasma GH. A dose of 0.067 microgram human pancreatic (hp) hpGHRF(1-40)OH/kg body wt 3 days after HST increased plasma GH to 55 ng/ml from a control period mean of 5 ng/ml (P less than 0.04). On Day 8, HST calves received two injections of 0.067 microgram hpGHRF/kg body wt at 3-hr intervals, with feeding 70 min after the first injection. During two preinjection control periods, basal GH averaged less than 4 ng/ml and increased to 17 (P less than 0.02) and 9 (P less than 0.04) ng/ml immediately after the first and second injection of hpGHRF, but the response declined over the 8-day period after surgery. On Days 19 and 20, the HST calves were infused iv with 0.033 and 0.067 microgram somatostatin(SS)-14 (SRIH)/kg body wt, during which a pulse injection of 0.067 microgram hpGHRF/kg body wt was administered. GH increased to 9 and 5 ng/ml during the 0.033- and 0.067-microgram SRIH infusions after GHRF; no somatotropic rebound was observed after the SRIH was discontinued as was seen in the animals while the hypothalamic-hypophysial connections were intact. Five and six months after HST the responses to two analogs of rat hypothalamic GHRF were similar to those in SOC calves. These results indicate that HST calves responded to exogenous GHRF with an abrupt increase in plasma GH, but GH response to GHRF during SRIH infusion was greatly inhibited.

Somatostatin as a physiological regulator of pulsatile growth hormone secretion.

Somatostatin plays an important role in the regulation of the episodic and ultradian rhythm of growth hormone (GH) secretion. Passive immunization of rats with specific antibodies to the 14 and 28 amino acid sequences caused a significant GH elevation. The fact that somatostatin antiserum was unable to block episodic GH surges indicates that this hormone's release must be regulated by a dual mechanism. Indeed, GH-releasing factor (GRF) seems to be instrumental in the maintenance of pulsatile GH secretion. Moreover, exogenous GRF induced a further GH increase predominantly during the period of active secretion. Neutralization of endogenous somatostatin eliminated this time-dependent effect, indicating that this peptide blocks periodical spontaneous GH release. Food deprivation and changes in glucose homeostasis virtually obliterate the ultradian GH rhythm. In this context, peripheral somatostatin seems to play an important role. Also the central GRF/somatostatin interplay is responsible for a short-loop feedback control on pituitary somatotrops.

Tissue and plasma distribution of exogenous growth hormone-releasing factor analogue (GRF1-29NH 2) after intravenous, subcutaneous and intraperitoneal injection in the rat

1. The administration of 125I-labelled growth hormone-releasing factor (GRF) analogue 1-29NH 2 by intravenous, subcutaneous or intraperitoneal injection to rats leads to rapid (i.v.) or slow (s.c. and i.p.) increases in plasma radioactivity followed by extensive breakdown of the peptide. 2. Tissues possessing GRF-like immunoreactivity such as gastric antrum (but not fundus), duodenum and ileum showed in vivo specific uptake of 125I-GRF probably mediated by vasoactive intestinal peptide (VIP) receptors. 3. Pituitary (the primary target organ for GRF) but neither thyroid nor parathyroid exhibited specific uptake of 125I-GRF.

Effects of neonatal administration of monosodium glutamate on plasma growth hormone (GH) response to GH-releasing factor in adult male and female rats

Female and male rats were treated with monosodium glutamate (MSG; 4 mg/g b.wt.) as neonates and the capability of the pituitary gland to secrete growth hormone (GH) in response to an intravenous injection of human GH-releasing factor (GRF) was evaluated under pentobarbital anesthesia on 109 days of life. Immunoreactive GRF content in the pituitary stalk-median eminence tissue in MSG-treated rats was less than 20% of that of control. A significant dose-dependent plasma GH response was observed after the administration of two doses of human GRF (0.25 and 1 μg/kg b.wt.,i.v.) in both control and MSG-treated rats. The responses between MSG-treated and control rats were comparable in female rats, but they were significantly reduced in male MSG-treated rats. These results show that the pituitary's responsiveness to exogenous GRF is well preserved in MSG-treated rats despite prolonged and severe depletion of endogenous GRF and there exists a sex difference in the effect of MSG on GH secretion elicited by GRF.

Growth Hormone-Releasing Factor Stimulates Milk Production and Sustains Growth Hormone Release in Holstein Cows

Serum growth hormone was determined in lactating cows following repeated intravenous injections of growth hormone-releasing factor. A given dose was injected every 4h for 24h in a 4 (cow)×4 (d) Latin square. Growth hormone increased similarly above controls after 10, 20, or 40μg releasing factor/100kg body weight. In another experiment the effects on lactational performance and growth hormone responses of cows to repeated injections of releasing factor for 10 d were determined in a 2 (cow)×2 (period) Latin square crossover. Administration of 20μg releasing factor/ 100kg body weight to 16 Holstein cows (lactating 4.5 to 7.5 mo) every 4-h for 10 d increased milk yield from 25.4 to 27.7kg/d and increased total fat, protein, and lactose 11% above controls. Releasing factor did not affect milk composition or feed intake. Peak growth hormone response to releasing factor was similar between d 1 (19.9ng/ml) and 10 (24.4ng/ml). Exogenous growth hormone-releasing factor administered to lactating Holstein cows at the doses tested: 1) increases growth hormone consistently, although the response is not dose dependent, 2) is galactopoietic, 3) causes an apparent increase in feed to milk conversion, and 4) increases growth hormone to at least the same magnitude on d 10 as on d 1.

Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. II. GH and PRL release-inhibiting effects of the opioid kappa receptor agonists bremazocine and U-50,488.

An analysis of the GH release-inhibiting action of the opioid kappa receptor agonists bremazocine and U-50,488, established earlier, was attempted by testing the agonists against activation of GH secretion by morphine or clonidine in male rats bearing right atrial cannulae for serial blood sampling and drug delivery. Both kappa agonists inhibited the effect of subsequent administration of clonidine in a dose-related manner. Bremazocine was approximately ten times more potent than U-50,488, a ratio corresponding to the known affinities of the two compounds for the kappa receptors. The inhibiting action of bremazocine was more strongly reversed by the preferential kappa receptor antagonist Mr-2266 than by naloxone, neither of which interfered with the GH-stimulating effect of clonidine. Bremazocine, however, did not alter the activation of GH secretion by exogenous growth hormone releasing factor. Thus, the inhibiting effect of bremazocine and probably U-50,488 seems to be derived from stimulation of the kappa receptors which in turn activates a GH release inhibiting mechanism of unknown identify which, however, does not involve release of somatostatin. Both kappa agonists also inhibited the effect of morphine, but in this case U-50,488 was approximately hundred times less effective than bremazocine. Since bremazocine and U-50,488 are antagonists of the delta receptors, which seem to mediate the GH-releasing effect to morphine, their inhibiting effect in this instance may be related to this property rather than to an action on the kappa receptors. Bremazocine, but not U-50,488, was also highly effective in inhibiting stimulation of PRL secretion by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone (GH) response to GH-releasing factor in adult female rats treated with monosodium glutamate during the neonatal period

Plasma GH response to human GH-releasing factor (GRF) was examined in adult female rats that had been treated with monosodium glutamate (MSG ; 4 mg/g BW, sc) for 5 days during the neonatal period. Rats given MSG had reduced nasal-anal length and revealed obesity compared to the control rats. Five months after MSG treatment, when the animals were killed by decapitation, it was found that their immunoreactive GRF content in the pituitary stalk-median eminence tissue was less than 20% of that of the control group and their anterior pituitary weight had decreased. However, the concentration of GH had not altered.Under pentobarbital anesthesia, basal plasma GH levels were significantly reduced in MSG-treated rats as compared to the control rats. A significant dose-dependent plasma GH response was observed after the administration of two doses of human GRF (0.25 and 1 μg/kg BW, iv) in the control group and MSG-treated rats. The responses among MSG-treated rats did not differ from those in the control rats.These results show that the pituitary's responsiveness to exogenous GRF is well preserved in MSG-treated rats despite prolonged and severe depletion of endogenous GRF.