Administration Of Growth Hormone-releasing Factor Research Articles

Effects of long‐term growth hormone‐releasing factor treatment on growth, feed conversion efficiency and dry matter intake in growing female buffaloes (Bubalus bubalis)

Effects of long-term growth hormone-releasing factor (GRF) on growth performance, feed conversion efficiency (FCE) and dry matter intake (DMI) were studied in growing buffaloes. Twelve female Murrah buffaloes of 6-8 months of age were divided into two groups of six each on the basis of their body weights so that the average body weights of the groups did not differ (p > 0.05). Animals of each group were administered intravenously with either sterile distilled water (control group) or equal volume of GRF solution containing 10 mug GRF (1-44)-NH2/100 kg body weight (treatment group) at fortnight interval from week 6 (5-week pre-treatment period) for 36 weeks (weeks 6-42 treatment period). Thereafter a 10-week post-treatment period was added. All the animals were weighed consecutively 2 days in a week and the average body weight of the two observations in the week was thus considered for further calculation. Dry matter intake was recorded daily. Average daily gain, FCE and DMI/100 kg body weight were also calculated. Plasma progesterone was estimated in the samples collected twice a week at 3-4-day intervals to assess whether either group had begun ovarian cycles. It was found that ADG and FCE were higher (p < 0.01) in GRF-treated animals during treatment and even 10-week post-treatment period. Interestingly, total DMI was not different (p > 0.05) between the groups during treatment period but found to be lower in GRF treated animals during post-treatment period. The DMI/100 kg body weight was lower (p < 0.01) in GRF-treated animals during treatment and even after cessation of treatment for 10 weeks. The GRF administration for long-term increased (p < 0.05) plasma progesterone. Plasma progesterone concentrations suggest that no animal from either group reached puberty till the end of the experiment. In conclusion, repeated GRF administration for longer term decreased (p < 0.01) DMI/100 kg body weight and increased (p < 0.01) FCE and enabled the animals to grow faster.

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 Selection for Milk Yield on Growth Hormone Response to Growth Hormone Releasing Factor in Growing Holstein Calves

Bull and heifer calves (n=81) from genetic lines of Holstein cows that differed by more than 4000kg milk/305-d lactation were used to determine effects of selection for milk yield on growth hormone (GH) response to a GH releasing factor (GRF) analog. Calves received GRF (4μg/100kg BW) on 10, 56, 140, 196, 252, and 364±3 d of age. Jugular blood samples (n=15) were obtained from −30 to 120min relative to GRF administration. Area under the GH response curve (0 to 60min, AUC60) was quantified after subtracting mean prechallenge GH concentrations. Data were analyzed for effects of line, age, gender, and their interactions with PROC MIXED of SAS for repeated measures and incorporated the spatial power law for unequally spaced data with age as the repeated effect. Means were considered different when P<0.05. Prechallenge GH concentrations did not differ between lines, were greater in bulls than heifers (4.6 vs. 3.7ng/ml), and decreased with age. The AUC60 decreased with age but did not differ between lines. Heifers responded more to GRF than bulls (1550 vs. 1336ng×min/ml). Peak GH concentration decreased with age and was less in bulls than heifers (54.7 vs. 62.1ng/ml) but did not differ between lines. Although plasma GH has been identified as an inheritable trait, we conclude the GH variables measured in this study were not useful in predicting genetic merit of calves from these substantially different lines of cows.

Short Communication: Growth Hormone Response to Somatostatin-28 and Growth Hormone-Releasing Factor in Dairy Heifers

In an attempt to investigate the role of somatostatin-28 (SRIF-28) in modulating growth hormone (GH)-releasing factor (GRF)-induced GH release in dairy cattle, we assigned Holstein heifer calves (n=12) to receive 0, 10, and 20μg of SRIF-28/100kg of BW (0, 10, 20) in conjunction with administration of 3μg of GRF/100kg of BW. Administration of 10 or 20μg of SRIF-28 reduced GRF-induced GH release, because areas under the response curves during 30min after GRF administration were less when cows received those dosages compared with receiving 0. Some evidence of a dose response was observed because serum GH concentrations increased from 15 to 20min after GRF administration when animals received 10μg, but continued to decrease when animals received 20μg of SRIF-28. We conclude that, in contrast to studies with SRIF-14, pituitary GH release is very sensitive to inhibitory effects of SRIF-28 when used in as little as a fivefold molar excess. Additional experimentation is necessary to determine whether equimolar concentrations of SRIF-28 are effective in altering GRF-induced GH release. Further, these results give rise to speculation that SRIF may be involved in physiological mechanisms mediating well-documented genetic influences on GH concentrations in dairy cattle.

Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: New cause of growth hormone insensitivity in humans

The effects of metabolic acidosis on growth hormone and IGF-1 are poorly understood. We investigated the effects of chronic metabolic acidosis (induced by administration on NH4Cl, 4.2 mmol/kg body wt/day) on the growth hormone/IGF-1 endocrine axis in 6 normal male volunteers during metabolic balance conditions. NH4Cl administration resulted in hyperchloremic metabolic acidosis with plasma bicarbonate decreasing from 25 +/- 0.4 to 15.5 +/- 0.9 mmol/liter (P < 0.001). Metabolic acidosis significantly decreased serum IGF-1 concentration from 45 +/- 6 to 33 +/- 6 nmol/liter (P = 0.002), while serum IGF binding protein 3 concentration was not affected significantly. The growth hormone response to growth hormone releasing factor administration (1 microgram per kg body wt, intravenous bolus) was enhanced significantly during acidosis. The IGF-1 response to growth hormone administration (0.1 U kg body wt subcutaneously, every 12 hr for 48 hr) was blunted significantly during acidosis. Apparent endogenous serum half-life and metabolic clearance rates of growth hormone were not altered significantly by acidosis. Metabolic acidosis in humans results in a significant decrease in serum IGF-1 concentration without a demonstrable effect on IGF binding protein 3, and is related to a resistance to the hepatocellular action of growth hormone. The primary defect in the growth hormone/IGF-1 axis occurs via an impaired IGF-1 response to circulating growth hormone with consequent diminution of normal negative feedback inhibition of IGF-1 on growth hormone, as evidenced by the exaggerated growth hormone response to growth hormone releasing factor administration.

Regulation of Pituitary Growth Hormone-Releasing Factor (GRF) Receptor Gene Expression by GRF

We examined how growth hormone-releasing factor (GRF) regulated pituitary GRF receptor gene expression in the conscious rat. GRF receptor mRNA levels were significantly increased by immunoneutralization of endogenous GRF with its specific antiserum. This effect was dose dependent and the maximum level was 3.8-fold higher than that in control rats. A similar rise in GRF receptor gene expression was obtained by the depletion of noradrenaline, a neurotransmitter thought to stimulate GRF release, and was reversed by 87% by the repeated administration of synthetic GRF. These results indicate that pituitary GRF receptor gene expression was up- or down-regulatedin vivoin the absence or presence of GRF, respectively.

Inhibition of GH in maternal separation may be mediated through altered serotonergic activity at 5-HT2A and 5-HT2C Receptors

The hyposecretion of growth hormone (GH) in maternal separation (MS) of rat pups is remarkably similar to the specific suppression of GH secretion to evocative tests in infants diagnosed with Reactive Attachment Disorder of Infancy (RADI). Growth hormone-releasing factor (GRF) and somatostatin (SS) provide opposing regulation of GH secretion, and both are modified by noradrenergic and serotonergic stimuli in neonatal and adult rats. In this study, GRF administration reversed MS-induced suppression of GH secretion in 10-day-old pups, but this action of GRF was prevented by pretreatment with cyproheptadine (Cypro), a serotonergic antagonist. The normalization of GH secretion after return to the dam was not altered by pretreatment with SS. Indirect 5-HT agonists, fluoxetine (FLX) and 5-HTP, both stimulated GH secretion in 10-day-old pups. All mixed serotonin- and 5-HT1A-receptor agonists suppressed GH secretion in 10-day-old pups. Antagonists Cypro and ketanserin (Ket) suppressed FLX-induced GH secretion. In contrast, only Cypro suppressed 5-HTP-induced GH secretion. Maternal separation inhibited GH secretion stimulated by 5-HTP, but not by FLX. The serotonergic pathway acting on 5-HT2A receptors may be obligatory for GRF-mediated stimulation and is sensitive to inhibition by Cypro. In addition, a Ket-sensitive serotonergic parallel pathway acting on 5-HT2C receptors may also stimulate GH secretion by acting on GRF or SS. However, only the obligate 5-HT2A pathway appears to be suppressed in MS. These data and observations by others indicate that specific suppression of GH secretion in MS may derive from a reduction in GRF release through noradrenergic neurons, possibly impinging upon serotonergic terminals in the hypothalamus. This study may also provide insight into mechanisms by which GH secretion is suppressed in humans with RADI.

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.

Effects of synthetic growth hormone-releasing factor in women treated with gonadotrophin

To evaluate the effects of synthetic growth hormone-releasing factor (GRF) in women with idiopathic infertility who were treated with human menopausal gonadotrophin (HMG), 13 women with this condition were randomly assigned to undergo treatment with HMG-GRF (500 micrograms twice daily) or HMG-placebo. Conception occurred in four of six women (14 cycles) who received HMG-GRF and in one of seven women (22 cycles) who received HMG-placebo. No difference was found in the amount of HMG and the duration of HMG required to induce ovulation between the two groups of patients. The overall serum growth hormone and insulin-like growth factor I concentrations were higher in the GRF than in the placebo group. No difference was found in serum oestradiol or inhibin concentrations between the two groups. Our results suggest that in women with idiopathic infertility, administration of GRF does not decrease the duration or the amount of HMG required to induce ovulation. However, it appears that in this small group concomitant treatment with GRF increases the pregnancy rates in women who are treated with HMG (4/14 cycles compared with 1/22 cycles).

Endogenous pulsing and stimulated release of growth hormone in dairy calves of high and low genetic merit

AbstractFifty-five calves aged 105 days of age, of both sexes, belonging to two genetic groups (H, high or L, low) differing in their predicted breeding value (PBV) by 78 kg for fat plus protein yield, were individually penned for 3 weeks with the final 2 weeks on a diet designed to provide energy close to their maintenance requirements. The calves were then cannulated in the jugular vein and blood was sampled every 15 min for 25 h. Following this a growth hormone releasing factor (GRF) preparation was administered on up to four occasions, being one of (per kg live weight) either 0·2 or 0·4 μg GRF (treatments SGRF or DGRF respectively) or 0·2 μg thyrotropin releasing hormone (TRH). On each occasion blood samples were taken at −15, 4, 8,12,16, 20 and 45 min relative to the time of administration and up to four further occasions, one prior to and three within 32 min of administration. Samples were assayed for growth hormone (GH).GH concentration of troughs prior to an episode of GH release was 1·19-fold greater in H compared with L calves with concentrations decreasing to 0·9 of their previous values each h. Trough and peak concentrations had repeatabilities of 0·21 and 0·26 respectively (both P &lt; 0·05). There was no association between PBV and either peak concentrations, number of pulses (4·84 per 25 h) or mean GH concentration (13·3 μg/l).GH released was only 1·11-fold greater after DGRF than SGRF. The difference in the regression coefficients for PBV between SGRF and DGRF was small, as it was for the difference between coefficients for the two sexes. The pooled coefficient was 0·00342 loge units per kg (s.e. 0·00157; P&lt; 0·05) indicating a 1·31-fold greater response in H than in L calves. The correlation between responses to SGRF and DGRF was 0·482 and the repeatability of SGRF was 0·338; a pooled repeatability was estimated as 0·362(P &lt; 0·01). The regression of GH release on PBV for TRH was 0·00345 (s.e. 0·00330). For all secretagogues, response depended on prior concentrations.It was concluded that GH release following GRF administration was positively related to PBV in dairy calves and response was moderately repeatable; furthermore, although aspects of endogenous secretion may be related to PBV they suffer from measurement difficulties.

Serum growth hormone in and semen characteristics of proven AI dairy sires after administration of growth hormone-releasing factor

A growth hormone-releasing factor (GRF) analog was administered at 11, 22 and 33 μg 100 kg−1 to proven dairy sires of varying genetic merit for production traits. Administration of GRF increased mean GH concentrations, but the area under the response curve was not different among the three dosages, nor were there differences between genetic groups overall. However, the maximum GH concentration following the administration of 11 μg 100 kg−1 was greater among superior sires. None of semen motility, sperm concentration or total sperm were affected through an entire spermatogonic cycle. Key words: GRF, growth hormone, semen, dairy bulls

Effects of administration of growth hormone-releasing factor to sows during late gestation on growth hormone secretion, reproductive traits, and performance of progeny from birth to 100 kilograms live weight.

The effects of growth hormone-releasing factor (GHRF) injections to sows during late gestation were investigated in two experiments. In the first one, four treatments were applied to eight catheterized sows according to two 4 x 4 Latin squares: oral administration of 2 mg of pyridostigmine, a cholinesterase inhibitor, per kilogram of BW (PYR group); i.m. injection of 50 micrograms of GHRF/kg BW (GHRF group); a combination of the pyridostigmine and GHRF treatments (PYR+GHRF); or i.m. injection of glucose (control). Pyridostigmine slightly increased the plasma concentration of growth hormone (GH). Growth hormone responses to GHRF and PYR+GHRF treatments were similar, with significantly elevated GH concentrations from 5 to 240 min after GHRF injection. In the second experiment, 36 sows were allocated to two treatments at 102 d of gestation. Until farrowing, they were injected twice daily with 50 micrograms of GHRF/kg BW (GHRF group) or isotonic glucose (control). The DM, N, fat, and energy content of 24 pigs per group was determined at weaning at 22 d. Six pigs per litter had ad libitum access to feed until slaughter at 100 kg BW and their carcasses were evaluated. Treatment with GHRF increased pregnancy duration (114.8 vs 113.6 d, P less than .05), weight of pigs at 13 d (3.69 vs 3.54 kg, P less than .05) and at weaning (5.74 vs 5.48 kg, P less than .05), and improved pig survival (86 vs 71%, P less than .05). Lipid (on a DM basis) and energy contents of the pigs slaughtered at weaning were significantly higher in the GHRF group than in the control group (14.4 vs 12.5% and 2,178 vs 2,029 kcal/kg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of prepartum administration of growth hormone-releasing factor on somatotropin, insulin-like growth factor I, milk production, and postpartum return to ovarian activity in primiparous beef heifers.

Forty-one primiparous beef heifers were used over 2 yr to evaluate the effect of prepartum administration of a growth hormone-releasing factor analog (GRF-A) or growth hormone-releasing factor (GRF(1-29)-NH2) on somatotropin (ST), insulin-like growth factor I (IGF-I), milk production, heifer BW, and postpartum (PP) return to ovarian activity. Beginning on d -11 +/- 1 from parturition, heifers were administered (s.c.) GRF-A ([desNH2-Tyr1,D-Ala2,Ala15]GRF(1-29)-NH2, 2.5 micrograms/kg; Yr 1) or GRF(1-29)-NH2 (12.5 micrograms/kg; Yr 2) (GRF; n = 17) or vehicle (CON; n = 24) for seven consecutive days. Blood samples were collected at 20-min intervals from -60 to 300 min from the first and fourth injections. Samples were also collected at 20-min intervals for 6 h on d 25 and 69 +/- 1 PP. Area under the curve of ST (nanograms.minute-1.milliliter-1) was greater (P less than .01) in GRF than in CON heifers (9,671 +/- 677 vs 2,611 +/- 237). Increases in ST after GRF-A or GRF(1-29)-NH2 were similar. On d 25 +/- 1 PP, frequency of ST release (pulses per 6 h) was greater (P less than .01) in CON (3.3 +/- .2) than in GRF (2.1 +/- .2) heifers. Milk production was similar (P greater than .1) for the two treatments. Heifer BW loss from d -16 to 81 after parturition was greater (P less than .01) in GRF (88 +/- 5) than in CON (68 +/- 5) heifers. Postpartum return to ovarian activity (progesterone greater than 1 ng/mL for two consecutive weeks) was delayed (P less than .05) in GRF (97 +/- 14) vs CON (71 +/- 8) heifers. After accounting for variation due to treatment and year, a negative (P less than .02) correlation (r = -.39) was detected between concentrations of IGF-I during the first 30 d PP and PP interval to ovarian activity. These results indicate that prepartum administration of GRF altered the release pattern of ST after parturition and was associated with greater PP BW loss and delayed PP return to ovarian activity in heifers.

Chronic administration of growth hormone-releasing factor increases wound strength and collagen maturation in granulation tissue

The effects of chronic administration of growth hormone-releasing factor (GRF) on wound healing were studied in rats. Cutaneous wound strength was measured by tensometry at 5, 10, and 14 days postwounding in rats implanted with a slow-release pellet which contained a compressed mixture of a fatty acid and [desamino Tyr 1, d-Ala 2, Ala 15]hGRF(1–29)NH 2 or the fatty acid alone. There was a significant increase in wound tensile strength in GRF-treated rats compared to controls at each measurement: Day 5, 130 ± 12 vs 97 ± 14 g; Day 10, 402 ± 18 vs 280 ± 11 g; Day 14, 830 ± 17 vs 614 ± 14 g ( P < 0.01 for each value). Granulation tissue obtained from subcutaneously implanted polyvinyl alcohol sponges encased in silicone tubing was also studied. The amount of collagen deposited in the granulation tissue was estimated by measuring the hydroxyproline (Hyp) content of sponges retrieved 5, 10, and 14 days postinsertion from GRF-treated and control rats. Hyp content (nmole/mg sponge) was similar in both treated and control animals at each measurement: Day 5, 1.7 ± 0.2 vs 2.2 ± 0.2; Day 10, 31.9 ± 4.1 vs 26.7 + 0.4; and Day 14, 41.6 ± 7.3 vs 38.5 ± 4.4. Hyp/proline, Hyp/glycine, and glycine/total amino acid ratios, evaluated after 10 days, were also similar in both groups. Collagen from the granulation tissue of sponges retrieved after 14 days from treated and control rats was studied by electron microscopy (magnifications, 7,100 and 22,720). The intercellular spaces in the sponges of the control rats were sparsely covered by collagen fibrils, in contrast to the intercellular spaces in the sponges of the treated rats, which were completely filled with collagen fibrils. These results demonstrate that chronic administration of GRF for 14 days increases wound strength during the early stage of healing in rats. In addition, GRF does not stimulate collagen deposition in granulation tissue, but accelerates collagen maturation instead. We postulate, therefore, that this effect is responsible for the enhanced cutaneous wound strength seen at 10 and 14 days postwounding in GRF-treated rats.

Effect of hypothalamic administration of growth hormone-releasing factor (GRF) on feeding behavior in rats

To examine the role and working site of growth hormone-releasing factor (GRF) in feeding behavior, we first tested the effect of the intracerebroventricular (i.c.v.) injection of GRF on food intake after 24 h of food deprivation. Cumulative food intake was measured 1, 3 and 6 h after injection. A lower dose of GRF stimulated food intake in a dose dependent manner (3h; GRF100pmol8.64 ± 1.06g vs saline5.50 ± 0.60g, P < 0.05), while a higher dose (1 nmol, 500 pmol) suppressed food intake (3h; GRF1mol2.65 ± 0.70g vssaline5.50 ± 0.60g, P < 0.01). Second, the effect of i.c.v. injection of 100 pmol of GRF on peripheral metabolites was examined. The subsequent levels of plasma insulin, glucagon, glucose and non-esterified fatty acid showed no significant difference from those of saline administration. Third, the effect of microinjection of GRF (5 pmol) into several hypothalamic areas on food intake was examined. Injection into the ventromedial hypothalamic nucleus (VMN) stimulated food intake (3h;GRF5pmol10.32 ± 1.04g vs saline6.92 ± 0.32g, P < 0.05), but no significant effect was observed following injection either into the lateral hypothalamic area (LHA), paraventricular nucleus (PVN) or medial preoptic area (MPOA). Finally, we tested the stimulatory effect of GRF on food intake in bilateral VMN lesioned rats. I.c.v. injection in these animals had no more significant effect on food intake than did saline injection in VMN lesioned rats (3h;GRF100pmol6.27 ±0.87g vs saline5.34 ± 0.44g). These results suggest that administration of a low dose of GRF centrally enhances feeding behavior and that the VMN is one of the working sites of this effect.

Effects of active immunization against somatostatin (SRIF) and/or injections of growth hormone-releasing factor (GRF) during gestation on hormonal and metabolic profiles in sows

The hormonal responses of gestating sows to immunization against somatostatin conjugated to bovine serum albumin (SRIF-IMM) and/or injections of growth hormone-releasing factor (GRF) were studied with thirty-eight second parity sows. Immunization against bovine serum albumin (BSA-IMM) was used as control. First immunizations were done on day 30 and boosters were given on days 44, 58, 72, 86 and 100 of gestation. Injections of GRF (9 mg of GRF (1–29)NH 2 per injection) or saline were given at 0800, 1400 and 2000 hr daily from day 90 of gestation until parturition. Mean body weights of sows at 85 and 110 d of gestation were 196.3 and 210.5 kg, respectively (SE = 0.8). Jugular blood samples were collected from 0740 hr to 1100 hr at 20 min intervals on days 90, 101 and 112 of gestation. On day 112, additional samples were collected from 1340 hr to 1700 hr and from 2140 hr to 2300 hr. At 112 d of gestation, antibody titers against SRIF (% binding, 1:150 dilution) were higher (P<0.01) for SRIF-IMM (13.5%) vs BSA-IMM (0.95%) sows. There was no effect of SRIF-IMM nor was there a GRF by SRIF-IMM interaction on any variable measured (P>0.05). Injections of GRF increased (P<0.01) the area under the curve (AUC) for growth hormone (GH; 305 vs 1623 ng/min/ml). The increase was greater as days of injection increased (P<0.05). Administration of GRF did not affect prolactin (Prl) AUC (P>0.05). There was no effect of time of injection on GH or Prl AUC (P>0.05). There was no effect of treatments on free fatty acids (FFA), glucose or insulin (P>0.05) but insulin-like growth factor I (IGF-I) concentrations increased in GRF-treated sows (P<0.01; 66 vs 101 ng/ml). Concentrations of FFA and IGF-I increased (P<0.01) as gestation advanced. Treatment with GRF increased weight gain of sows during late lactation (P<0.01). In conclusion, GH AUC was increased by GRF injections but not by SRIF-IMM in gestating sows. Concentrations of FFA, glucose and insulin were not altered by either treatment, but those of IGF-I were increased by GRF.

Pregnancy following combined growth hormone—pulsatile GnRH treatment in a patient with hypothalamic amenorrhoea

A patient with hypothalamic amenorrhoea and a poor response in terms of pituitary growth hormone (GH) to acute administration of growth hormone-releasing factor has been treated with pulsatile gonadotrophin-releasing hormone (GnRH) combined with GH to induce ovulation. GH was administered daily until signs of ovulation were detected. The luteal phase was supported by pulsatile GnRH only. Combined treatment gave an improved follicular recruitment, higher plasma levels of 17 beta-oestradiol and an earlier ovulation, compared to the previous cycle with pulsatile GnRH only. The result was a twin pregnancy which ended with the birth of two healthy male babies. The role of GH in potentiating the ovarian response to gonadotrophins, as well as the GH secretion abnormalities associated with dysfunctions of the hypothalamic - pituitary - gonadal axis, might provide a rationale for combined GH and pulsatile GnRH treatment in such patients.

Insulin-like growth factor-I concentration in Holstein female cattle: variations with age, stage of lactation and growth hormone-releasing factor administration

Plasma insulin-like growth factor-I (IGF-I) concentrations were monitored in Holstein females through different periods of their growth, lactation and after acute or chronic growth hormone-releasing factor (GRF) administration. Plasma samples were radioimmunoassayed using a human IGF-I antibody after a 24 hr incubation in a HC1(.1N)-glycine(.2M) buffer (pH 2). In a first study, IGF-I concentrations were measured in Holstein females of different ages and(or) stages of lactation (n = 6 per group). The IGF-I concentrations in newborn calves (102.0 ± 11.3 ng/ml) markedly decreased (P<.01) in 1 mo old animals (50.2 ± 7.1 ng/ml), then increased (P<.01) to 137.0 ± 5.1 and 137.4 ± 11.0 ng/ml in 6 and 10 mo old heifers, respectively. In dairy cows, IGF-I concentrations were low 24 hr post-partum (44.7 ± 7.6 ng/ml) and then increased (P<.05) to remain stable throughout lactation (91.3 ± 4.9, 92.8 ± 12.9, 96.1 ± 7.6, 90.7 ± 8.8 ng/ml at 2, 3, 6 and 9 mo of lactation, respectively). There was a further increase (P<.05) to 113.7 ± 3.1 ng/ml during the dry period. In a second trial, blood samples were collected from lactating dairy cows every 2 hr for 24 hr following a sc injection of saline (n = 4) or human (h) GRF (1–29)NH 2 (10 μg/kg BW, n = 4). The IGF-I peak concentration was reached on average 10 hr after the GRF injection and was higher (P<.01) in treated cows than in control cows (135.4 vs 86.9 ± 16.2 ng/ml). In the last trial, daily sc injections of 10 μg of hGRF(1–29)NH 2 per kg BW to dairy cows (252 days of lactation) for 57 days, which increased milk production by 14% (2 kg/day), also increased (P<.01) IGF-I concentration: 127.1 ± 5.3 and 118.0 ± 1.6 vs 90.7 ± 4.7 and 96.0 ± 5.0 ng/ml on days 29 and 57 of treatment for treated (n = 9) and control (n = 8) cows, respectively. Thus, the IGF-I concentration in dairy cattle varies with age and stage of lactation, and is increased by GRF administration in lactating dairy cows.

Effects of Intracerebroventricular Administration of Growth Hormone-Releasing Factor and Corticotropin-Releasing Factor on Somatostatin Secretion into Rat Hypophysial Portal Blood

To clarify the regulatory mechanisms for the secretion of somatostatin (SRIF) from the hypothalamus, the effects of intracerebroventricular (i.c.v.) administration of growth hormone-releasing factor (GRF) and corticotropin-releasing factor (CRF) on SRIF secretion into hypophysial portal blood were examined in pentobarbital-anesthetized male rats. Neither the concentration of SRIF in portal plasma nor the secretion rate of SRIF was changed after i.c.v. administration of 0.9% saline. Administration of 10 ng or 5 micrograms human GRF i.c.v. produced a significant increase in the portal plasma concentration and secretion rate of SRIF. Likewise, 5 micrograms CRF significantly increased the portal plasma concentration and secretion rate of SRIF. These results suggest that the neuropeptides GRF and CRF centrally influence SRIF secretion into hypophysial portal blood.

Growth hormone-releasing factor on growth hormone secretion in prepubertal calves.

The effects of iv administration of growth hormone-releasing factor (GRF) on growth hormone (GH) release and on nitrogen metabolism were measured in prepubertal calves. Crossbred beef heifers (111 kg) were used in a Latin square design to test the effects of 0, 0.01, 0.033, 0.067, and 0.1 microgram human pancreatic (hp) GRF [hpGRF (1,40)OH]/kg body wt on plasma GH concentrations. When they were given doses of 0.067 and 0.1 microgram hpGRF/kg body wt, plasma GH increased (P less than 0.05) within 5-15 min, compared with injections of control buffer, and then returned to preinjection concentrations. The response to 0.067 microgram hpGRF/kg body wt every 3 hr for 42 hr was studied in five heifers (137 kg body wt). The animals responded to 50% of the GRF injections with an increase in plasma GH during every 6-hr period measured. Nitrogen retention, hormone concentrations, and weight gain were measured in five bull calves (90 kg body wt) administered 0 or 0.067 microgram Nle rat hypothalamic GRF (1,29)NH2/kg body wt every 4 hr for 10 days. Metabolic parameters were interpreted to indicate an anabolic response to GRF even though increases of 16% in nitrogen retention, 23% in plasma somatomedin C concentrations, and 36% in weight gain with pulsatile GRF treatment were variable and statistically similar to those of controls. These results indicate that GRF induces peak GH secretion within 15 min in prepubertal calves and that calves can respond to multiple injections of GRF with an increase in plasma GH.