Altered LH Research Articles

P-32 MANAGEMENT OF A RARE COMPLICATION IN TYPE 1 DIABETES WITH EXTREME LIVER ENLARGEMENT AND GROWTH FAILURE

Abstract Clinical Case A 21 year old single male presented with growth failure, delayed puberty, and significant liver enlargement attributed to glycogen deposition, a rare complication observed in some children and young adults with Type 1 Diabetes Mellitus (T1DM), irrespective of glycemic control. In his initial visit (Sep 5, 2020):Height: 144 cm, Weight: 40 kg. The patient’s uncontrolled diabetes and growth failure were notable. In the follow-up visits (Oct 4, 2020 - May 20, 2024), the patient exhibited fluctuating glycemic control (HbA1c ranging from 9.7% to 12.0%), variably elevated liver enzymes (ALT and AST), and concerning lipid profiles, with triglycerides peaking at 905 mg/dL. Growth parameters remained below the expected range for age and sex, indicating persistent growth failure. Laboratory tests highlighted uncontrolled diabetes, hypertriglyceridemia, and liver enzyme elevation. Endocrinological assessments revealed low testosterone levels with slightly altered FSH and LH, pointing to a hypogonadotropic pattern. The persistent high HbA1c levels (>10%) indicated poor glycemic control, complicating the patient’s liver condition and growth failure. The treatment regimen focused on intensive insulin therapy to manage diabetes, using combinations of NovoRapid, Tresiba, Ryzodec (aspart+degludec), and Apidra (Glulisine insulin). Lipid profile management included Lipanthyl (Fenofibrate) and Crestor (Rosuvastatin). Nutritional support was indicated with Nutrigen syrup aiming to address growth failure and possible micronutrient deficiencies. Despite the comprehensive management approach, challenges in achieving optimal glycemic control were apparent with the latest HbA1c at 9.7%. However, some improvement in liver enzymes and lipid profile was noted. Growth failure and delayed puberty remain significant concerns requiring ongoing multidisciplinary care. Conclusion This case underscores the complexity of managing rare complications of T1DM like extensive liver enlargement due to glycogen deposition, in conjunction with growth failure and delayed puberty. It highlights the necessity of an integrated therapeutic strategy focusing not only on glycemic control but also on the management of associated metabolic derangements and hormonal imbalances. Further research into targeted treatments for such rare complications is warranted. Managing patients with T1DM who develop rare complications such as extensive liver enlargement, growth failure, and delayed puberty is challenging. A holistic and tailored approach is essential for improving patient outcomes, underlining the crucial role of continuous monitoring, adjustment of therapeutic strategies, and multidisciplinary care.

Lame cows have a subdued hypothalamus-pituitary axis as revealed by LH release in response to exogenous endocrine challenges

Lameness is a serious concern in cows due to its multilevel effects and increasing incidences. The ability of anterior pituitary and hypothalamus to release LH, a prime reproductive hormone, is unknown in lame cows. Our study tested this ability by exogenous endocrine challenge using Buserelin acetate (GnRH analogue) and estradiol valerate (EV). The study included moderately lame (L; n=7) either cyclic (LC; n=3) or anestrus (LA; n=4); and normal cyclic, non–lame (NL; n=5) cows. Progesterone blocks LH release, so it was lowered by injecting PG in cyclic cows. After 14 h, all cows were given a walk for 5 min and immediately thereafter injected with 0.008 mg GnRH and 4 h later with 1 mg of EV. Blood plasma progesterone, cortisol and LH were quantified, periodically. There was a significant delay in the onset (105.0 vs 75.0±7.0 vs 54.0±9.0 min) and duration (22.5±5.3 vs 80.0±10.8 vs 117.0±2.7 min) of LH surge in LA vs LC vs NL cows; the surge was absent in two LA cows. The altered LH profile was attributed to a 3 fold (in L) vs 1.6 fold (in NL) rise in cortisol. LH released (ng/ml) in response to EV was also low in LA (31.5±2.4) and LC (69.9±7.2) than NL (79.2±7.0) cows. In conclusion, lame cows subjected to walk exhibited reduced pituitary response to release LH following exogenous GnRH as also a reduced ability of hypothalamus to stimulate LH release in response to exogenous estradiol.

The polymorphic insertion of the luteinizing hormone receptor “insLQ” show a negative association to LHR gene expression and to the follicular fluid hormonal profile in human small antral follicles

The luteinizing hormone receptor (LHCGR) has a little studied polymorphic 6 bp insertion (rs4539842/insLQ). This study has evaluated the insLQ polymorphism in relation to potential associations with hormonal characteristics of human small antral follicles (hSAFs).In total, 310 hSAFs were collected from 86 women undergoing fertility preservation. Analysis included hormonal profile of 297 follicular fluid (FF) samples and 148 corresponding granulosa cells samples were evaluated by qPCR for selected genes.Significantly reduced and non-detectable mRNA levels of anti-Müllerian hormone receptor II (AMHR2) and LHCGR, respectively, were observed for insLQ/insLQ compared to –/insLQ and the −/− genotypes. Moreover, LHCGR and CYP19a1 together with oestradiol and inhibin-B were significantly increased in –/insLQ compared to the −/− genotype. The homozygous insLQ genotype showed strong significant associations to GC specific genes LHCGR and CYP19a1, which may translate into significant changes in FF hormone profiles and an altered LH signaling.

Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome

Background: Loss-of-function mutations in immunoglobulin superfamily member 1 (IGSF1) cause an X-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise, variable prolactin deficiency and variable partial GH deficiency in childhood. The clinical features and gene expression pattern suggest a pivotal role for IGSF1 in the pituitary, but detailed knowledge on pituitary hormone secretion in this syndrome is lacking. We therefore aimed to study the 24-hour pituitary hormone secretion in male patients with IGSF1 deficiency. Methods: We collected blood samples every 10 min for 24 h in eight adult male IGSF1-deficient patients and measured circulating TSH, prolactin and gonadotropins. Deconvolution, modified cosinor and approximate entropy analyses were applied to quantify secretion rates, diurnal rhythmicity and regularity of hormone release. Results were compared to healthy controls matched for age and body mass index. Results: Compared to healthy controls, IGSF1-deficient patients showed decreased pulsatile secretion of TSH with decreased disorderliness and reduced diurnal variation. Basal and pulsatile secretion of FSH was increased by over 200%, while LH secretion did not differ from healthy controls. We observed a bimodal distribution of prolactin secretion, i.e. severe deficiency in three and increased basal and total secretion in the other five patients. Conclusion: The altered TSH secretion pattern is consistent with the previously hypothesized defect in thyrotropin-releasing hormone signaling in IGSF1 deficiency. However, the phenotype is more extensive and includes increased FSH secretion without altered LH secretion as well as either undetectable or increased prolactin secretion.

We-P11:210 Evaluation of novel phosphatidic acid derivatives as antagonists of platelet activation induced by the plaque lipid lysophosphatidic acid

Our objectives were to evaluate the acute effects of a controlled internal drug release (CIDR) insert containing 1.38 g of progesterone (P4) on the release of LH, follicular growth, and circulating concentrations of P4 in cows treated with GnRH at the time of CIDR insertion. Nonpregnant, lactating dairy cows (n = 27) were blocked by parity, predicted 305-d mature-equivalent milk production, and body condition score and randomly assigned to 1 of 3 treatments: (1) CIDR insertion concurrent with an injection of 200 µg of GnRH (n = 10; 2GP4); (2) CIDR insertion concurrent with an injection of 100 µg of GnRH (n = 10; 1GP4); and (3) injection of 100 µg of GnRH (n = 7; CON). Prior to onset of treatments, cows were submitted to a presynchronization protocol that consisted of a CIDR insert containing 1.38 g of P4 from d −7 to −2, 25 mg of PGF2α on d −2 and −1, and 100 µg of GnRH on d 0. Experimental treatments were applied on d 6, the early luteal phase of the estrous cycle. Concentrations of P4 in plasma were determined on d −2 and 0 and at 0, 15, 30, 60, 120, 240, 345, 600, and 1,200 min relative to treatment on d 6. Concentrations of LH were determined in plasma samples obtained at 0, 15, 30, 60, 120, 240, and 345 min relative to treatment on d 6. Ultrasonography examinations of ovarian structures were performed on d −2, 0, 2, and at 0, 600, and 1,200 min relative to treatment on d 6. Mean concentrations of P4 in the CON group (1.91 ± 0.28 ng/mL) were lower than in 2GP4 (3.40 ± 0.26 ng/mL) and 1GP4 (3.31 ± 0.24 ng/mL) groups, but concentrations in 2GP4 and 1GP4 were similar. Mean concentration of LH in response to the GnRH injection on d 6 was greatest in 2GP4 cows (3.08 ± 0.21 ng/mL) and did not differ between 1GP4 (2.23 ± 0.21 ng/mL) and CON (2.14 ± 0.25 ng/mL) cows. The diameter of the dominant follicle on d 6 was similar among treatments (2GP4 = 15.34 ± 0.50; 1GP4 = 15.31 ± 0.50; CON = 14.77 ± 0.62 mm). In conclusion, CIDR insertion concurrent with a 100- or 200-µg dose of GnRH neither altered GnRH-induced LH release nor had an acute effect on dominant follicle growth.

Calcitonin Expression in Rat Anterior Pituitary Gland Is Regulated by Ovarian Steroid Hormones

Gonadotroph-derived calcitonin-like peptide (pit-CT) is a potent inhibitor of lactotroph function. We investigated the effect of ovarian hormones on pit-CT mRNA expression in the anterior pituitary (AP) gland of cycling female rats. Levels of mRNAs for pit-CT, CT receptor, prolactin (PRL), and beta-LH during 4-d estrous cycle were determined. In a second study, the effects of estrogens and progesterone on pit-CT and PRL mRNA levels were investigated. In a third group, the effect of estrogen or progesterone depletion on pit-CT mRNA expression was studied. In a fourth group, the effect of passive pit-CT immunization on PRL and LH mRNA expression was examined. Pit-CT mRNA levels varied during estrous cycle. They were highest in diestrus, but lowest in the evening of proestrus. CT-receptor mRNA levels displayed smaller fluctuations. Estrogen repletion caused a decline in pit-CT mRNA expression in ovariectomized rats, but progesterone produced a marked increase. ICI 182,780 prevented the decline of pit-CT mRNA levels during late proestrus-estrus, but RU 486 attenuated pit-CT mRNA levels. Passive CT immunization in diestrus altered PRL and LH mRNA expression, and advanced the estrus cycle. These results suggest that pit-CT mRNA expression is regulated by ovarian hormones, and depletion of pit-CT advances their estrous cycle.

Reproductive abnormalities in human IGF binding protein-1 transgenic female mice.

The mechanisms responsible for reproductive abnormalities in transgenic female mice overexpressing human IGF binding protein-1 (IGFBP-1) in the liver have been investigated. At 2 months of age, none of these transgenic mice exhibited ovarian cyclicity. Genital tract and ovary tissue weights were reduced in transgenic mice, this weight reduction being disproportionate with the reduction of body weight. Examination of ovarian follicular population revealed a marked decrease in the number of corpora lutea and gonadotropin-dependent follicles, suggesting an alteration of terminal follicular growth and ovulation. Stimulation of ovaries by exogenous gonadotropins revealed that ovaries from transgenic mice ovulated less oocytes than nontransgenic mice. This lower responsiveness of ovaries from transgenic mice to gonadotropins was not associated with a decrease in FSH-, LH- or IGF-I receptor expression. Transgenic and nontransgenic mice have similar circulating LH and FSH concentrations at dioestrus, after castration, 46 h after equine CG administration, or 15 min after GnRH injection. However, LH concentrations were 8-fold higher in pituitaries from transgenic vs. nontransgenic mice. Moreover, the size of LH-immunoreactive cells was reduced and their number was increased, suggesting a subtle alteration of LH secretion. Overall, these data indicate that reduced fertility in transgenic female mice overexpressing human IGFBP-1 are mainly due to an alteration of terminal follicular growth leading to a decrease in natural and induced ovulation rate, likely due to an impairment of IGF-I action on follicular cells. Increased circulating IGFBP-1 concentrations may additionally lead to altered GnRH and LH pulsatility and thereby exacerbate the ovulation defect.

Functional integrity of ErbB-4/-2 tyrosine kinase receptor complex in the hypothalamus is required for maintaining normal reproduction in young adult female rats.

ErbB-1 tyrosine kinase receptors are necessary for maintaining female reproduction by modulating the release of LH-releasing hormone (LHRH). Changes in ErbB-1 signaling capacity in aging rats are linked to compromised reproduction. The interactive and synergistic nature of different members of ErbB receptors in mediating signal transduction exists in many cellular systems. Particularly, the interactions among ErbB-1 and ErbB-2 or ErbB-4 and ErbB-2 are known to be involved in the stimulation of LHRH secretion during sexual maturation. Thus, ErbB-4/-2 receptors may also play a role in maintaining reproduction during adulthood, and consequently, alteration in ErbB-4/-2 signaling capacity may contribute to compromised reproductive competence during aging. By in situ hybridization histochemistry, ErbB-4/-2 mRNAs were detected in the preoptic area (POA) and arcuate nucleus, which are important areas involved in the control of LHRH neuronal activity. RT-PCR analyses showed that levels of ErbB-4/-2 mRNA increased to a maximal value in the POA of young adult animals before the LH surge. However, no such increase was found in middle-aged female rats. The timing of the decrease in ErbB-4 mRNA in the median eminence-arcuate nucleus of middle-aged rats was delayed compared with that in young adult animals. Disruption of functional ErbB-4/-2 receptor complex by blocking ErbB-2 receptor synthesis in the hypothalamus via an infusion of ErbB-2 antisense oligodeoxynucleotide resulted in an estrous acyclicity in young adult rats. These results indicate that changes in ErbB-4/-2 gene expression and functional integrity of this ErbB-4/-2 receptor complex in the hypothalamus of middle-aged female animals may lead to an altered preovulatory LH release. Thus, the ErbB-4/-2 receptor complex is a physiological component necessary for maintaining female reproduction.

Obese Cycling Women Show Elevated Leptin and a Failure to Slow LH Pulse Frequency in the Mid-Luteal Phase

Objective and Design: Leptin has been recently implicated as an important metabolic mediator of the maturation of the GnRH pulse generator that occurs with puberty. Its role in other reproductive events associated with changing GnRH pulse frequency is less clear. To further define the influence of leptin and body weight on the neuroendocrinology of the menstrual cycle, we studied pulsatile LH secretion and leptin concentrations in obese, cycling women. We postulated that in addition to the well-known effect of body weight, leptin concentrations would be higher in the mid-luteal phase (vs follicular phase) of obese women and associated with altered LH pulse frequency when compared to normal-weight controls.

Temporal interrelationships among luteolysis, FSH and LH concentrations and follicle deviation in mares

The effect of altered LH concentrations on the deviation in growth rates between the 2 largest follicles was studied in pony mares. The progestational phase was shortened by administration of PGF2α on Day 10 (Day 0=ovulation; n=9) or lengthened by daily administration of 100 mg of progesterone on Days 10 to 30 (n=11; controls, n=10). All follicles ≥5 mm were ablated on Day 10 in all groups to initiate a new follicular wave. The interovulatory interval was not altered by the PGF2α treatment despite a 4-day earlier decrease in progesterone concentrations. Time required for growth of the follicles of the new wave apparently delayed the interval to ovulation after luteolysis. The FSH concentrations of the first post-ablation FSH surge were not different among groups. A second FSH surge with an associated follicular wave began by Day 22 in 7 of 11 mares in the progesterone group and in 0 of 19 mares in the other groups, indicating reduced functional competence of the largest follicle. A prolonged elevation in LH concentrations began on the mean day of wave emergence (Day 11) in the prostaglandin group (19.2 ± 2.2 vs 9.0 ± 0.7 ng/mL in controls; P<0.05), an average of 4 d before an increase in the controls. Concentrations of LH in the progesterone group initially increased until Day 14 and then decreased so that by Day 18 the concentrations were lower (P<0.05) than in the control group (12.9 ± 1.6 vs 20.2 ± 2.6 ng/mL). Neither the early and prolonged increase nor the early decrease in LH concentrations altered the growth profile of the second-largest follicle, suggesting that LH was not involved in the initiation of deviation. However, the early decrease in LH concentrations in the progesterone group was followed by a smaller (P<0.05) diameter of the largest follicle by Day 20 (26.9 ± 1.7 mm) than the controls (30.3 ± 1.7 mm), suggesting that LH was necessary for continued growth of the largest follicle after deviation.

Aging results in attenuated gonadotropin releasing hormone-luteinizing hormone axis responsiveness to glutamate receptor agonist N-methyl-D-aspartate.

Reproductive aging in the Brown Norway rat occurs because of testicular as well as hypothalamic-pituitary dysfunction. Excitatory amino acids (EAA) participate in the regulation of pulsatile secretion of hypothalamic GnRH and pituitary LH. In the present study, we studied the EAA-GnRH-LH axis for possible age-related alterations in prepubertal (35 days), young (3-4 months), middle-aged (12-13 months) and old (21-23 months) rats. In the first experiment, an intra-atrial cannula was implanted in rats of different ages to evaluate the pituitary response to small, physiological intravenous bolus administration of GnRH (0.5 or 1.0 nmol/100 g body weight). The results showed no age-related significant differences in in-vivo serum LH or FSH responsiveness to GnRH. In a second experiment, blood samples for the gonadotropins were withdrawn immediately before and 10 min after an iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 mg/kg, a dose that induces a physiological LH pulse in young rats). Administration of NMDA induced significant increases in LH and prolactin in all groups of animals (P<0.05) and a significant FSH response in young and middle-aged but not old rats. NMDA-induced LH, FSH and prolactin release was higher (P<0.05) in prepubertal rats than in all other age groups. Compared with young rats, NMDA-induced increase in plasma LH and prolactin was lower (P<0.05) in old rats. In the third experiment, to ascertain whether this reduced LH response to NMDA in old rats was exerted at the hypothalamic level, the effects of NMDA on GnRH release in vitro from preoptic area-medial basal hypothalamus (POA-MBH) fragments were compared among rats of different ages. GnRH efflux in response to NMDA was significantly attenuated with increasing age. GnRH release in vitro was higher in prepubertal and lower in old than in young rats (P<0.05). Lastly, we measured amino acid concentrations in hypothalamic tissue (POA-MBH fragments). Prepubertal rats had higher levels of glutamate and taurine than young rats. Significant reductions in glutamate and gamma-aminobutyric acid (GABA) levels were found in old compared to young rats. In conclusion, these results showed that the hypothalamic NMDA-GnRH-LH axis was altered in old rats. The decreased hypothalamic content of some of the EAA and the reduced responsiveness of GnRH neurons to NMDA (both in vivo and in vitro) may contribute to an altered LH pulsatile secretion observed in old rats.

The maturation of GABA A receptor-mediated control of luteinizing hormone secretion in immature male rats

In male rats, a GABA A receptor antagonist, bicuculline methiodide or an agonist, muscimol, was infused intravenously for 30 min into the male rat before (postnatal days 16–17 and days 30–31) and after (over day 45) the sexual maturation. Neither bicuculline nor muscimol infusion significantly altered serum LH concentrations at days 16–17. At the days 30–31 and after day 45, bicuculline infusion significantly increased and muscimol infusion significantly decreased serum LH. In conclusion, in male rats, the functional GABA A receptor system to inhibit the release of LH seems to be established before the sexual maturation, between 18 and 29 days of age.

Mechanisms of altered LH secretion in neonatally oestrogenized male rats

It is well known that the control of LH secretion depends on the steroid milieu during the postnatal period. In this study LH secretion was analysed in adult male rats injected neonatally with 500 micrograms oestradiol benzoate (1) after orchidectomy, (2) after selective elimination of androgens by destruction of Leydig cells with ethylene dimethane sulphonate (EDS), and (3) after removal in orchidectomized animals of Silastic capsules containing testosterone. In addition, (4) in vivo and in vitro LH secretion in response to LHRH agonist and antagonists, (5) the hypothalamic LHRH content, (6) the basal and stimulated in vitro LHRH release, and (7) the LH responses after administration of naloxone (2 mg/kg), alpha-methyl-p-tyrosine (alpha-MPT; 250 mg/kg), N-methyl-D-aspartic acid (NMDA, 15 mg/kg) or kainic acid (KA; 15 mg/kg) were also examined. Our data indicated that (1) the LH response after orchidectomy, after EDS administration and after removal of Silastic capsules containing testosterone was diminished in oestrogenized male rats, (2) the pituitaries from oestrogenized males retained responsiveness to LHRH, (3) hypothalamic LHRH content was reduced in oestrogenized males, but the hypothalamus from oestrogenized males released more LHRH than those of control groups both under basal conditions or after depolarization, (4) alpha-MPT decreased LH secretion only in oestrogenized males, and (5) NMDA and KA stimulated LH only in oestrogenized males. We conclude that in oestrogenized male rates the loss of sensitivity to the negative feedback action of testosterone on LH secretion was not due to decreased pituitary responsiveness to LHRH stimulation or to the inherent damage of LHRH neurones.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exogenous steroid hormones on the dominant follicle maintained by a Norgestomet implant in heifers

The maintenance of the dominant follicle during the follicular phase by a 9-d Norgestomet implant was used to study the effects of progesterone (P4), estradiol-17β (E2) and testosterone (T) on follicular turnover in heifers. From day 4 of Norgestomet treatment, heifers (n = 16) were injected daily for 4 d with corn oil (control), 150 mg P4, 10 mg E2 or 200 mg T (n = 4 per treatment). Follicular changes were monitored daily by ultrasonography. Plasma steroids and serum LH were measured by validated radioimmunoassays. In control heifers, dominant follicles were maintained during implantation and ovulated after implant removal. In both P4- and T-treated heifers, dominant follicles began to regress during the implant period and the dominant follicle from a new wave of follicles ovulated. In E2-treated heifers, dominant follicles regressed (3/4) and dominant follicles from the next wave ovulated. The dominant follicle became cystic in the fourth E2-treated heifer. Mean serum LH levels were suppressed (P &lt; 0.01) from 0.55 ± 0.01 ng mL−1 (mean ± SEM) in control to 0.21 ± 0.02, 0.19 ± 0.02 and 0.43 ± 0.02 in P4-, E2- and T-treated heifers, respectively. The number of LH pulses in 8 h was reduced (P &lt; 0.01) from 6.25 ± 0.75 in control to 2.00 ± 1.00 and 4.66 ± 0.35 in P4- and E2-treated heifers but not in T-treated heifers (6.33 ± 1.44). LH pulse amplitude (ng mL−1) was also suppressed (P &lt; 0.01) in P4-treated (0.10 ± 0.04) and E2-treated (0.09 ± 0.02) heifers when compared with control heifers (0.41 ± 0.04) but not in T-treated heifers (0.42 ± 0.17). Exogenous P4 and E2 caused regression of the Norgestomet-maintained dominant follicle, and this effect was associated with altered serum LH profile. Injection of T caused atresia of the dominant follicle without altering the LH profile. Key words: Dominant follicle, atresia, heifers, steroids, LH, ultrasound, E2, estradiol-17β; P4, progesterone; T, testosterone

Altered luteinizing hormone pulse frequency in early follicular phase of the menstrual cycle with luteal phase defect patients in women

To delineate the relationship between the pulsatile gonadotropin inputs in early follicular phase of the menstrual cycle and the P secretions by the corpus luteum in women. For measuring pulsatile release of gonadotropin, blood samples were drawn every 15 minutes for 24 hours in the early follicular phase. Daily blood samples were drawn for LH, FSH, E2, and P. The reproductive endocrine unit of a university hospital. Fourteen patients with luteal phase defect (LPD) and 12 normally cycling women. The length of follicular phase in LPD was significantly shorter than that of women with normal cycles. There were significant differences in LH pulsatile secretions and amplitudes in LPD patients when compared with those of women with normal cycles. Basal E2, PRL, and preovulatory E2 concentrations were not different between the two groups whereas the peak of P secretions in luteal phase was significantly decreased in LPD. These data suggest that LPD may result from the altered LH pulse frequency in early follicular phase of the menstrual cycle. Whether this increased LH pulse frequency results from an intrinsic disease of the pulse oscillator or to some event in the preceding cycle remains unknown. It is tempting to speculate that an increased LH pulsatile secretion in the early follicular phase of menstrual cycles in patients with LPD may down-regulate the LH secretion at midcycle, thereby lowering the LH surge, which in turn reduces the P secretion in luteal phase.

Timing of growth hormone injections and reproduction in gilts

Sixty-eight Yorkshire × Landrace gilts were selected at 85 kg body weight (BW) and exposed to a mature boar for 20 min d−1 to detect puberty. At the onset of puberty, gilts were allocated to receive daily intramuscular injections of porcine growth hormone (pGH, 90 μg kg−1 BW) from either 14 to 17 d (GH17, n = 22) or from 14 to 22 d (GH22 n = 22) after puberty, inclusively. A third group of gilts served as controls (n = 24) and received vehicle buffer. A single blood sample was obtained from each gilt on days 14, 17 and 20. Also, four gilts from each pGH treatment and eight control gilts were sampled at 15-min intervals for 8 h on day 16. Gilts were slaughtered 30 d after puberty at which time their ovaries were recovered for the determination of ovulation rate. Injection of pGH resulted in elevated serum concentrations of triiodothyronine, insulin and glucose (P &lt; 0.01). There was no significant (P &gt; 0.1) treatment effect on mean serum concentrations of LH or FSH. However, pGH treatment tended (P = 0.1) to increase LH pulse frequency and to decrease (P = 0.01) LH pulse amplitude. The incidence of a second estrus was reduced (P &lt; 0.01) in GH22 compared to control gilts, with GH17 being intermediate (72.7 vs. 90.9 vs. 100% for GH22, GH17 and control gilts, respectively). Ovulation rate was not affected by pGH treatment (15.1 vs. 14.3 vs 14 0 for GH22, GH17 and control gilts, respectively). The present data confirm an adverse effect of pGH on ovarian function and suggest that an altered LH pulsatility may be involved. Key words: Gilts, growth hormone, estrus, endocrinology

Follicle stimulating hormone - secreting pituitary adenoma: inappropriate secretion and effect of pulsatile luteinizing hormone releasing hormone analogue (buserelin) administration

A patient with an FSH secreting pituitary adenoma is reported. Elevated FSH and serum free alpha-subunit (SU) with low levels of LH and testosterone (T) were found. Immunostaining showed the presence of alpha-SU, FSH-beta and LH-beta subunits. LHRH analogue (buserelin) was administered in a pulsatile manner, by portable computerized infusion pump sc for ten days. During the first 24 h of treatment FSH, LH (p less than 0.001) and T (p less than 0.01) rose significantly. Ten days later, the expected desensitization phenomenon did not occur, but further increases of T (8.4 +/- 2.6, mean +/- SD, vs 17.4 +/- 4.1 nmol/l, p less than 0.001) and FSH (58.9 +/- 9.6 vs 70.7 +/- 3.8 mlU/ml, p less than 0.001) were registered. LH decreased (12.5 +/- 2.4 vs 7.1 +/- 0.6 mlU/ml, p less than 0.001) at day 10, but remained higher than basal level (5.0 +/- 0.6, p less than 0.001). Free alpha-SU also rose (2.8 +/- 0.4 vs 4.4 +/- 1.7 mlU/ml, p less than 0.001) after ten days of treatment. The chronic stimulatory effect of analogue on LH with a lack of desensitization suggests tumorous secretion despite a partially preserved negative feedback of testosterone. Low basal LH levels, in some patients with FSH secreting tumors may not be due to tumor mass effect, but rather may be the consequence of altered LH production and/or secretion by the tumor. Although buserelin may not have a therapeutic effect, it is of use in differential diagnosis of hypergonadotropinemia.

Advancement of Postnatal Pulsatile Luteinizing Hormone Secretion in the Bull Calf by Pulsatile Administration of Gonadotropin-Releasing Hormone during Infantile Development1

The transition from infantile to prepubertal development in bull calves coincides with the onset of postnatal LH secretion following differentiation of pituitary gonadotropes. Increased pulsatile secretion of hypothalamic GnRH may contribute to maturational development of the hypothalamic-pituitary axis. To evaluate the role of GnRH pulse frequency in mediating changes in pituitary response that may lead to altered LH release, serum LH concentrations in Holstein bull calves treated with exogenous GnRH were examined. Nine calves received 200 ng GnRH for 5 min every hour from 1-6 wk of age (GnRH-T), while 5 animals served as controls. Weekly through 6 wk of age, jugular venous blood was collected every 10 min for 8 h. Blood samples from GnRH-T animals were taken during 2 exogenous GnRH pulses followed by 6 h of sampling without exogenous GnRH. Mean serum LH concentrations were greater (p less than or equal to 0.01) in GnRH-T calves than in controls at 2 through 6 wk of age. LH pulse height did not change in either group during the study period. However, LH pulse frequency in GnRH-T calves increased with age (P less than or equal to 0.01), and at 4-6 wk of age, the rate of pulsatile LH secretion was greater (p less than or equal to 0.01) in GnRH-T calves than in controls. Pituitary LH content increased 2.4-fold after GnRH infusion (p less than or equal to 0.01); this increase was associated with a doubling of the pituitary LH-beta mRNA concentration found in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Further evidence against dopamine deficiency as the cause of inappropriate gonadotropin secretion in patients with polycystic ovary syndrome.

Previous studies suggested that a relative dopamine (DA) deficiency may explain the altered LH secretory dynamics that occur in patients with polycystic ovary syndrome (PCO). These studies included findings of decreased urinary excretion of homovanillic acid (HVA), a metabolite of DA, and increased urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), the major brain metabolite of norepinephrine. To further explore the role of DA in these patients, disulfiram (250 mg) was administered daily for 2 weeks to alter the conversion of DA to norepinephrine and to increase both peripheral and central DA in patients with PCO and in normal women. LH pulse frequency and amplitude and the serum LH response to GnRH were assessed before and during disulfiram administration. A dopaminergic effect during disulfiram administration was evidenced by a decrease in serum PRL in the PCO patients and an increase in urinary HVA excretion and a decrease in the ratio of 3-methoxy-4-hydroxyphenylglycol to HVA in urine in both groups (all P less than 0.05). This increase in DA did not significantly alter the serum estrogen level, the mean serum LH level, LH pulse amplitude, or serum LH responses to GnRH in either the PCO patients or the normal women. These data suggest that increasing endogenous DA does not correct the inappropriate gonadotropin secretion characteristic of PCO and places further doubt on the importance of DA in explaining the altered LH secretory dynamics in these patients.

Effects of aging and illness on the pituitary testicular axis in men: qualitative as well as quantitative changes in luteinizing hormone.

Decreased testicular function occurs as a concomitant of aging in men and is accentuated by the presence of systemic illness. Previous studies identified an intrinsic Leydig cell defect, as reflected by high LH to testosterone ratios and impaired hCG responsiveness in older men. This study questioned whether a qualitative change in LH secretion, as reflected by secretion of LH with an altered ratio of biological to immunological LH (B/I) activity, might occur during aging. To examine this possibility, we measured the levels of plasma LH by RIA and rat interstitial cell testosterone bioassay in 67 men, ranging from 20-80 yr of age. Mean LH levels measured by immunoassay were similar in healthy men older than 40 yr [11.4 +/- 1.0 (+/- SE) mIU/ml; n = 22] and those younger than 40 yr (9.4 +/- 0.6; n = 18; P less than 0.01). Mean bioactive LH levels were also similar (30.0 +/- 4.8 vs. 36.7 +/- 3.3). LH B/I ratios, however, were significantly lower in older men (2.52 +/- 0.33) compared to those in younger (4.10 +/- 0.34; P less than 0.01) men. Regression analysis confirmed the expected inverse relationship of B/I ratio with age (r = -0.47; P less than 0.01) and plasma testosterone with age (r = -0.35; P less than 0.05). Systemic illness independently lowered B/I LH ratios. Systemically ill men over 40 yr of age had lower ratios (1.05 +/- 0.08; n = 27) than age-matched healthy men (2.52 +/- 0.33; n = 22; P less than 0.01). The significant changes in B/I ratio among subgroups reflected modest changes in LH immunoactivity and larger alterations in LH bioactivity in certain subgroups. These findings indicate that the qualitative nature of LH secreted by the pituitary, as reflected by altered LH B/I ratios, may vary as a function of aging and illness in men.