Adrenocorticotropin Hormone Administration Research Articles

Impact of adrenocorticotropin hormone administration on the endocrinology, estrus onset, and ovarian function of weaned sows.

Chronic stress affects the reproductive health of mammals; however, the impact of adrenocorticotropin hormone (ACTH) level elevation during chronic stress on the reproduction of weaned sows remains unclear. In this study, nine weaned sows with the same parturition date were randomly divided into control group (n = 4) and ACTH group (n = 5). Each group received intravenous administration of ACTH three times daily for 7 days. Blood samples were collected every 3 h after injection. A radioimmunoassay was used to measure the concentrations of cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4) and estradiol-17β (E2) in the blood. Estrus was determined according to changes in the vulva and the boar contact test. The mRNA expressions of glucocorticoid receptor, FSH receptor, LH receptor (LHR) in the corpus luteum (CL) were detected by qRT-PCR. The results showed that ACTH administration substantially delayed the initiation of estrus and the pre-ovulatory LH peak. The sows of control group ovulated within 10 days and the ovulation rate was 100%, while it was 60% in the ACTH group. Two sows of ACTH group showed pseudo-estrus. The E2 concentrations significantly decreased in the ACTH group at 36 h, 42 h and 66 h of the experimental period. The P4 concentrations in the ACTH group significantly decreased at 132, 138, and 147 h of the experimental period. ACTH significantly reduced the LHR mRNA expression in CLs. In conclusion, long-term repeated ACTH administration affects the endocrinology, estrus onset, and ovarian function of weaned sows.

Paradoxical Results after Inadvertent Use of Cosyntropin [Adrenocorticotropin Hormone (1-24)] Rather than Acthrel (Ovine Corticotropin Releasing Hormone) during Inferior Petrosal Sinus Sampling

The use of ovine corticotropin releasing hormone (oCRH) maximizes the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome (CS). oCRH is marketed as ACTHrel and, understandably, may be confused with cosyntropin [ACTH (1-24)]. The inadvertent substitution of synthetic ACTH(1-24) for oCRH (ACTHrel) during IPSS may cause unexpected and misleading results. The aim of this report is to raise awareness of the potential confounding results created when synthetic ACTH(1-24) is mistakenly used during IPSS. We present 3 patients treated at 3 different centers with ACTH-dependent CS in whom ACTH(1-24) was mistakenly substituted for oCRH (ACTHrel) during IPSS. In all patients, there was an abrupt and unexpected decrease in plasma ACTH in the inferior petrosal sinus (IPS) samples after presumptive stimulation with oCRH. Re-evaluation of the patients' pharmacy records confirmed that synthetic ACTH(1-24) had been used rather than oCRH during each procedure. Because "sandwich" immunometric assays for ACTH measure the entire pool of endogenous ACTH, the administration of synthetic ACTH(1-24) artifactually decreases the endogenous plasma ACTH(1-39) measurement by binding only to the N-terminal antibody raised against ACTH(1-17) and not to the C-terminal antibody raised against ACTH(34-39). This results in a lack of a detectable sandwich complex and explains the apparent reduction in ACTH concentration. An abrupt decrease in ACTH during IPSS suggests that synthetic ACTH(1-24) rather than oCRH (ACTHrel) has been administered. The labeling of oCRH as ACTHrel poses a potential patient safety problem about which endocrinologists, interventional radiologists, and pharmacists should be aware.

Circulating Corticosterone Reaction to Restraint and Adrenocorticotropin Hormone Administration in White Leghorns Selected for Immune Response Traits

Corticosterone plasma concentration was measured in a random-bred control line and in 3 White Leghorn chicken lines previously selected over 9 generations for 3 different in vivo immune responses: high antibody response to Newcastle disease virus vaccine 3 wk after vaccination (ND3), high cell-mediated immune response (response to phytohemagglutinin, PHA), and high phagocytic activity measured as carbon clearance (CC). The objective of the study was to estimate if selection on immune response had an effect on the response to stress assessed by measures of corticosterone concentration before and after physical stress or adrenocorticotropin hormone injection and if the effect was dependent on the immune response trait that had been selected for, by joint analyses of immune responses and concentrations. The mean values of plasma corticosterone measures did not differ between lines, indicating that selection for different high immune responses had little effect on response to stress. Within line, however, significant negative correlations (−0.46 ≤ r ≤ −0.39) were found between cell-mediated immunity and corticosterone plasma concentrations in 3 of the 4 lines. Moreover, in the line selected for high antibody titers (ND3-L), corticosterone levels were positively correlated to ND3 (r = 0.41 and 0.47) and negatively correlated to CC (r = −0.48).

Comparison of the hypothalamic–pituitary–adrenal axis in MDR1‐1Δ and MDR1 wildtype dogs

AbstractObjective: To evaluate the hypothalamic–pituitary–adrenal (HPA) axis in MDR1‐1Δ (dogs with the MDR1 mutation associated with ivermectin sensitivity) and MDR1 wildtype dogs.Design: Prospective study.Setting: Institutional vivarium.Animals: Seven healthy Collie dogs.Measurements: MDR1 genotyping was used for allocation of dogs to 1 of 2 groups: dogs homozygous for the wildtype MDR1 allele (MDR1 wildtype) and those homozygous for the MDR1‐1Δ mutation (MDR1 mutant). Blood samples were obtained for determination of cortisol and adrenocorticotropin hormone (ACTH) concentrations under basal conditions, before and after ACTH administration, and before and after dexamethasone administration.Main results: Significant differences were identified between the MDR1 mutant and MDR1 wildtype groups. Basal plasma cortisol concentrations and cortisol concentrations after ACTH administration were significantly lower in MDR1 mutant dogs as compared with MDR1 wildtype dogs. Plasma ACTH concentrations after dexamethasone administration were significantly lower in MDR1 mutant dogs as compared with MDR1 wildtype dogs.Conclusions: Results suggest that P‐glycoprotein (P‐gp) plays a role in regulation of the HPA axis. Furthermore, it appears that the HPA axis in MDR1 mutant dogs that lack P‐gp is suppressed compared with MDR1 wildtype dogs. This finding may explain some clinical observations in breeds known to harbor the MDR1 mutation including Collies, Shelties, Australian Shepherds, and others. There is a clinical impression that many of these dogs have worse outcomes in response to stress and, at times, respond poorly to appropriate therapy. HPA axis suppression, secondary to the MDR1 mutation, could result in a relative adrenal insufficiency (RAI) state during times of stress or illness. Further studies are required to determine the relationship between the MDR1 genotype and RAI.

Low serum allopregnanolone levels in girls with precocious pubarche

Allopregnanolone, a neuroactive steroid, increases during pubertal development and high concentrations are present in subjects with precocious puberty. The aim of the present study was to evaluate serum allopregnanolone levels in girls with precocious pubarche (PP). Basal gonadotropins and steroid hormones were assessed in 17 girls with PP, 22 girls with central precocious puberty (CPP), 25 girls with normal puberty at the same pubertal stage of CPP ones, and 17 prepubertal girls. Adrenocorticotropin hormone (ACTH) and gonadotropin-releasing hormone (GnRH) stimulation tests were performed in all subjects with PP, and in 12 out of 22 with CPP. All girls with normal puberty underwent to GnRH test, while ACTH test was performed in 17 out of 25. Basal dehydroepiandrosterone sulfate (DHEAS) concentrations resulted significantly higher in PP and normal pubertal girls than in prepubertal ones. Allopregnanolone, gonadotropins and estradiol levels were significantly lower in PP group with respect to CPP ( P < 0.05), while they were comparable among PP, normal pubertal and prepubertal groups. After ACTH administration, allopregnanolone concentrations significantly increased in all groups ( P < 0.05). After GnRH stimulation, its levels significantly increased in CPP and normal pubertal controls ( P < 0.05), while no incremental rise was found in PP girls. In conclusion, our study shows that in girls with PP basal and GnRH-stimulated levels of allopregnanolone are significantly lower than in CPP girls. These data suggest that this neurosteroid may be considered a new marker of pubertal development.

DHEA, PREG and their sulphate derivatives on plasma and brain after CRH and ACTH administration.

The term neurosteroids applies to steroids that are synthesized in the nervous system, either de novo from cholesterol or from steroid hormone precursors. RIA was used to determine plasma and brain levels of the neurosteroids pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their sulfate derivatives (PREG-S and DHEA-S) in male and female rats after administration of two typical stress hormones: corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH). In all cases, the parameters measured were detectable in plasma and brain. PREG, PREG-S, and DHEA increased significantly in plasma and brain after CRH and ACTH administration in males and females. Because neurosteroids play an important role in mammalian physiology, including that of humans, stress situations may alter the physiological functions regulated by these neurosteroids.

An Alternative Method for Delivering Adrenocorticotropin Hormone in Birds

In birds, intrajugular injection (ij) of exogenous adrenocorticotropin hormone (ACTH) has been used to challenge adrenocortical tissue when investigating various dynamics of the hypothalamic–pituitary–adrenal (HPA) axis. Although this method has been shown to deliver ACTH efficiently, ij injection can be difficult and potentially damaging to the bird, especially to young birds and small species. Intramuscular (im) injection has been shown to be an alternative method for delivering ACTH to large birds; however, small songbirds have relatively less muscle mass in which to absorb im injections and, in very small birds, even small needles may injure the delicate muscle tissue. Therefore, intraperitoneal (ip) administration of ACTH was investigated as a means of avoiding the potential problems associated with ij and im injections when conducting adrenocortical pathway studies on small birds. Dark-eyed Juncos, Junco hyemalis, were first treated with dexamethasone to suppress the endogenous signal cascade for corticosterone release. Twelve hours later, birds were sampled for baseline corticosterone concentration and then immediately given an ip injection of either ACTH or physiological saline. A second blood sample was taken from all birds 30 min later to assess the effectiveness of ip ACTH administration on adrenocortical tissue. While saline-treated birds showed no significant increase in endogenous plasma corticosterone in response to the capture and handling protocol, ACTH-treated birds showed a significant increase in plasma corticosterone concentration, illustrating the effectiveness of the ip administration of exogenous ACTH. The adrenocortical response of ACTH-treated birds was similar in magnitude and rate of increase to that found in free-living, noninjected Juncos. Intraperitoneal injection of ACTH is thus a valid alternative to ij and im injections when challenging adrenocortical tissue in small birds.

Effects of CRH and ACTH administration on plasma and brain neurosteroid levels.

The 3alpha-hydroxy ring A-reduced metabolite of progesterone, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) is among the most potent known ligands of the gamma aminobutyric acid (GABA) receptor, designated GABA-A, in the central nervous system. We determined by RIA serum levels of progesterone (PROG), 5-alpha-dihidroprogesterone (DHP) and allopregnanolone in male and female rats after corticotropin releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) administration. Allopregnanolone was undetectable in plasma and brain of control males but detectable in plasma and brain of males injected with CRH and ACTH and of control and similarly treated females. Allopregnanolone increased in the plasma and brain after CRH and ACTH administration in all cases. The data demonstrate that the administration of CRH plus ACTH results in a rapid increase of the neuroactive steroid allopregnanolone in the brain of males and females to levels known to modulate GABA-A receptor function. Thus, stress could regulate neurosteroid biosynthesis via the hormones ACTH and CRH.

Production and secretion of C-19 steroids by rat and guinea pig adrenals

The concentrations of C-19 steroids were measured in guinea pig and rat adrenals before and after castration as well as after stimulation with adrenocorticotropin hormone (ACTH). Characterization of adrenal C-19 steroids was also carried out by isolation with high-performance liquid chromatography and gas chromatography/mass spectrometry (GC/MS). From radioimmunoassay (RIA) data, androstenedione (4-DIONE) and 11β hydroxyandrostenedione (11β-DIONE) were the major C-19 steroids found in guinea pig adrenals, and castration induced a decrease of 4-DIONE levels only while all other C-19 steroids remained unchanged. In rat adrenals, the major C-19 steroids were 4-DIONE and testosterone, and they were also markedly inhibited after castration. With the exception of 11β-DIONE, all other C-19 steroids in circulation were eliminated after castration in both animals species. After ACTH administration in the guinea pig, adrenal 4-DIONE and 11β-DIONE levels were markedly stimulated, while an increase of only 11β-DIONE was observed in plasma. In the rat, ACTH had a small stimulatory effect on adrenal 52-androstane-3α, 17β-diol (3α-DIOL) and plasma 11β-DIONE levels. Analysis of guinea pig adrenal steroids by GC/MS confirmed the presence of C-19 steroids in adrenals (namely, 4-DIONE and 11β-DIONE) while, in t fie rat, this could not he confirmed. Our data indicate that production of C-19 steroids occurs in guinea pig adrenals, and 11β-DIONE is the major C-19 steroid as well as the only C-19 steroid secreted into the circulation. In the rat, the production of C-19 steroids detected by RIA is not supported by GC/MS data. (Steroids 55:360–365, 1990)