Increased Serum Luteinizing Hormone Levels Research Articles

Exposure to di-n-octyl phthalate during puberty induces hypergonadotropic hypogonadism caused by Leydig cell hyperplasia but reduced steroidogenic function in male rats

Humans are exposed to phthalates ubiquitously, which may threaten health. However, whether di-n-octyl phthalate can prevent pubertal sexual maturity is still elusive. In this study, male Sprague Dawley rats (age 35 days) were treated daily by gavage with 0, 10, 100, and 1000 mg/kg body weight of di-n-octyl phthalate from day 35 to day 49 after birth. Di-n-octyl phthalate significantly reduced serum testosterone levels at doses of 100 and 1000 mg/kg, but increased serum luteinizing hormone levels of 1000 mg/kg and decreased testosterone/luteinizing hormone ratio at ≥10 mg/kg, without affecting serum follicle-stimulating hormone levels. Di-n-octyl phthalate significantly induced Leydig cell hyperplasia (increased number of CYP11A1-positive Leydig cells) at 100 and 1000 mg/kg. Di-n-octyl phthalate down-regulates the gene expression of Cyp11a1, Hsd3b1 and Insl3 in individual Leydig cells. Di-n-octyl phthalate can also reduce the number of sperm in the epididymis. Di-n-octyl phthalate increased phosphorylated AKT1/AKT2 without affecting their total proteins, but increased the total protein and phosphorylated protein of ERK1/2 and GSK-3β. Primary immature Leydig cells isolated from 35-day-old rats were treated with 0–50 μM di-n-octyl phthalate for 3 h. This phthalate inhibited androgen production under basal, LH-stimulated, and cAMP-stimulated conditions by 5 and 50 μM in vitro via down-regulating Cyp11a1 expression but up-regulating Srd5a1 expression in vitro. In conclusion, di-n-octyl phthalate induces hypergonadotropic hypogonadism caused by Leydig cell hyperplasia but reduced steroidogenic function and prevents sperm production.

Erythropoietin-producing hepatocellular receptor A7 restrains estrogen negative feedback of luteinizing hormone via ephrin A5 in the hypothalamus of female rats.

We have previously shown that systemic injection of erythropoietin-producing hepatocellular receptor A7 (EPHA7)-Fc raises serum luteinizing hormone (LH) levels before ovulation in female rats, indicating the induction of EPHA7 in ovulation. In this study, we aimed to identify the mechanism and hypothalamus-pituitary-ovary (HPO) axis level underlying the promotion of LH secretion by EPHA7. Using an ovariectomized (OVX) rat model, in conjunction with low-dose 17β-estradiol (E2) treatment, we investigated the association between EPHA7-ephrin (EFN)A5 signaling and E2 negative feedback. Various rat models (OVX, E2-treated OVX, and abarelix treated) were injected with the recombinant EPHA7-Fc protein through the caudal vein to investigate the molecular mechanism underlying the promotion of LH secretion by EPHA7. Efna5 was observed strongly expressed in the arcuate nucleus of the female rat by using RNAscope in situ hybridization. Our results indicated that E2, combined with estrogen receptor (ER)α, but not ERβ, inhibited Efna5 and gonadotropin-releasing hormone 1 (Gnrh1) expressions in the hypothalamus. In addition, the systemic administration of EPHA7-Fc restrained the inhibition of Efna5 and Gnrh1 by E2, resulting in increased Efna5 and Gnrh1 expressions in the hypothalamus as well as increased serum LH levels. Collectively, our findings demonstrated the involvement of EPHA7-EFNA5 signaling in the regulation of LH and the E2 negative feedback pathway in the hypothalamus, highlighting the functional role of EPHA7 in female reproduction.

Correcting imbalance of sex hormones by a phosphodiesterase 5 inhibitor improves copulatory dysfunction in male rats with type 2 diabetes

IntroductionSexual dysfunction is a common complication in men with type 2 diabetes and is often refractory to treatment. This study investigated the long-term influence of the phosphodiesterase 5 inhibitor (PDE5I)...

Primary aldosteronism in Klinefelter's syndrome: two cases.

SummaryPrimary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of luteinizing hormone (LH) receptor in patients with PA has been reported; however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a 2-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered.Learning points:The pathogenesis of primary aldosteronism is still unclear.Expression of luteinizing hormone receptor has been reported in aldosterone-producing adenoma.Serum luteinizing hormone, which is increased in patients with Klinefelter’s syndrome, might contribute to the development of primary aldosteronism.

SAT-420 Gonadotropin-Releasing Hormone Stimulates Luteinizing Hormone Exocytosis without Elevating Lhb Expression

Continuous but not pulsatile delivery of GnRH leads to marked down regulation of luteinizing hormone (LH) secretion and blockade of reproductive functions. However, the relationship between LH beta subunit gene (Lhb) expression and LH secretion has not been studied in detail. Here we studied the relationship between Lhb expression, LH release and intracellular LH content under different experimental paradigms. Experiments were performed in vivo and in vitro using female and male rats and in cultured rat pituitary cells. In vitro experiments included evaluation of Lhb expression during the prolonged absence of GnRH, influence of culture medium on gene expression, continuous vs repetitive GnRH application, and ELISA vs Western blot analysis of LH content. Experiments showed that Lhb expression declined progressively after pituitary removal and cell dispersion, indicating the loss of regulated gene expression. Addition of GnRH receptor agonists did not rescue Lhb expression, suggesting that other factor(s) account(s) for regulated gene expression. On the other hand, GnRH stimulated LH secretion in vitro, leading to gradual depletion of the secretory pool during continuous receptor activation. Inhibition of transcription by actinomycin D had only a minor effect on in vitro LH secretion, in contrast to cycloheximide, a protein synthesis inhibitor. In vivo administration of a GnRH receptor agonist was accompanied with a rapid increase in serum LH levels and a progressive depletion of the intrapituitary LH levels, without affecting Lhb expression. These results indicate that GnRH controls LH synthesis and exocytosis post-transcriptionally and that pulsatile GnRH release protects gonadotrophs from depletion of the LH secretory pool.

Aging and Declining Testosterone: Past, Present, and Hopes for the Future

As men age, serum testosterone (T) levels decline, whereas serum luteinizing hormone (LH) levels increase somewhat or remain unchanged. Age-related reductions in T levels may be associated with alterations in body composition; energy level; muscle strength; physical, sexual, and cognitive functions; and mood. The predominant contributor to the decline in serum T levels is the decreased ability of the aging testes to make T. As in humans, the Brown Norway rat demonstrates age-related reductions in serum T levels in the setting of unchanged or modestly increased serum LH levels. In this rat model, the ability of aged Leydig cells, the terminally differentiated T-producing cells of the testis, to produce T in response to LH stimulation is significantly diminished. This review begins with a discussion of what is known of the molecular mechanisms by which T synthesis declines with Leydig cell aging. It concludes with a brief history of T replacement therapy, current guidelines, controversies related to T replacement therapy in older men, and proposed future clinical directions.

Molecular cloning and functional characterization of the first non-mammalian 26RFa/QRFP orthologue in Goldfish, Carassius auratus

In this study, we used data mining approach to predict 26RFa/QRFP precursors from fish, amphibian, reptile and avian species and subsequently cloned a 26RFa/QRFP precursor cDNA from goldfish brain based on the predicted sequences information. The goldfish 26RFa/QRFP precursor cDNA encoded a propeptide of 168 amino acids (aa) with predicted signal peptide of 30 aa at N-terminal and putative mature peptides, including 26RFa (26 aa) and 7RFa (7 aa) located at the C-terminal. Multiple sequence alignment showed almost all of the 26RFa/QRFP mature peptides possessed KGGFXFRF-amide motifs (X = G, S, A or N) at their C-terminus, and the last three residues FRF were fully conserved across vertebrates, indicating that the evolutionary pressure has exerted to conserve several C-terminal amino acid residues among the known and predicted 26RFa/QRFP precursors. Real-time PCR revealed that 26RFa/QRFP gene was expressed abundantly in goldfish hypothalamus, optic tectum–thalamus and testis. The regulation of goldfish hypothalamic 26RFa/QRFP gene expression by negative energy balance and putative role of goldfish 26RFa/QRFP in the control of luteinizing hormone (LH) release were studied. Hypothalamic 26RFa/QRFP gene expression was pronouncedly increased at 4 days after food deprivation. Furthermore, intraperitoneal (IP) injection of synthesized goldfish 26RFa/QRFP at a dose of 1 μg/g bodyweight significantly increased serum LH levels at 1 h. However, LH levels were not significantly changed by IP injection of goldfish 26RFa/QRFP at lower dosage or at other time points (3 and 6 h), or by incubation of goldfish primary cell cultures. These results suggested that goldfish 26RFa/QRFP shared some similar features with its mammalian counterparts and partly exerted the regulatory function in energy homeostasis and hypothalamic–pituitary–gonadal (HPG) axis as observed in mammalian species.

Effects of galanin-like peptide on luteinizing hormone secretion in the rat: sexually dimorphic responses and enhanced sensitivity at male puberty

Reproductive function is exquisitely sensitive to adequacy of nutrition and fuel reserves, through mechanisms that are yet to be completely elucidated. Galanin-like peptide (GALP) has recently emerged as another neuropeptide link that couples reproduction and metabolism. However, although the effects of GALP on luteinizing hormone (LH) secretion have been studied, no systematic investigation on how these responses might differ along sexual maturation and between sexes has been reported. Moreover, the influence of metabolic status and potential interplay with other relevant neurotransmitters controlling LH secretion remain ill defined. These facets of GALP physiology were addressed herein. Intracerebral injection of GALP to male rats induced a dose-dependent increase in serum LH levels, the magnitude of which was significantly greater in pubertal than in adult males. In contrast, negligible LH responses to GALP were detected in pubertal or adult female rats at diestrus. Neonatal androgen treatment to females failed to "masculinize" the pattern of LH response to GALP. In addition, metabolic stress by short-term fasting did not prevent but rather amplified LH responses to GALP in pubertal males, whereas these responses were abrogated by pharmacological inhibition of nitric oxide synthesis. We conclude that the ability of GALP to evoke LH secretion is sexually differentiated, with maximal responses at male puberty, a phenomenon which was not reverted by manipulation of sex steroid milieu during the critical neonatal period and was sensitive to metabolic stress. This state of LH hyperresponsiveness may prove relevant for the mechanisms relaying metabolic status to the reproductive axis in male puberty.

Novel role of 26RFa, a hypothalamic RFamide orexigenic peptide, as putative regulator of the gonadotropic axis

The close link between reproductive function and body energy stores relies on a complex neuroendocrine network of common regulatory signals, the nature of which is yet to be fully elucidated. Recently, 26RFa was identified in amphibians and mammals as a conserved hypothalamic neuropeptide of the RFamide family, with a potent orexigenic activity. Yet, despite its proposed role as hypophysiotropic factor, the function of 26RFa in the control of pituitary gonadotropins and, hence, of the reproductive axis remains unexplored. In the present study, the effects of 26RFa on gonadotropin secretion were evaluated in the rat by a combination of in vitro and in vivo approaches. At the pituitary, 26RFa dose-dependently enhanced basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion from male and cyclic female rats. This effect was mimicked by the active fragment 26RFa(20-26), as well as by the related 43RFa peptide. Moreover, expression of the genes encoding 26RFa and its putative receptor, GPR103, was demonstrated in rat pituitary throughout postnatal development. In vivo, intracerebral injection of 26RFa evoked a significant increase in serum LH levels in cyclic and ovariectomized females; this response which was also observed after central injection of 26RFa(20-26) and 43RFa peptides, as well as after systemic administration of 26RFa. Conversely, central and systemic injection of 26RFa failed to significantly modify gonadotropin secretion in adult male rats, even after repeated administration of the peptide. In summary, we present herein novel evidence for the potential role of the orexigenic peptide 26RFa in the control of the gonadotropic axis, thus suggesting its potential involvement in the joint control of energy balance and reproduction, especially in the female.

Serum luteinizing hormone levels are markedly increased and significantly correlated with Δ 4-androstenedione levels in lean women with polycystic ovary syndrome

Lean women with polycystic ovary syndrome have markedly increased serum luteinizing hormone levels, which are significantly correlated with Delta(4)-androstenedione levels but not directly linked to insulin resistance.

In vitro and in vivo effects of ghrelin on luteinizing hormone and growth hormone release in goldfish.

We studied the in vitro and in vivo effects of octanoylated goldfish ghrelin peptides (gGRL-19 and gGRL-12) on luteinizing hormone (LH) and growth hormone (GH) release in goldfish. gGRL-19 and gGRL-12 at picomolar doses stimulated LH and GH release from dispersed goldfish pituitary cells in perifusion and static incubation. Incubation of pituitary cells for 2 h with 10 nM gGRL-12 and 1 or 10 nM gGRL-19 increased LH-beta mRNA expression, whereas only 10 nM gGRL-19 increased GH mRNA expression. Somatostatin-14 abolished the stimulatory effects of ghrelin on GH release from dispersed pituitary cells in perifusion and static culture. The GH secretagogue receptor antagonist d-Lys(3)-GHRP-6 inhibited the ghrelin-induced LH release, whereas no effects were found on stimulation of GH release by ghrelin. Intracerebroventricular injection of 1 ng/g body wt of gGRL-19 or intraperitoneal injection of 100 ng/g body wt of gGRL-19 increased serum LH levels at 60 min after injection, whereas significant increases in GH levels were found at 15 and 30 min after these treatments. Our results indicate that, in addition to its potent stimulatory actions on GH release, goldfish ghrelin peptides have the novel function of stimulating LH release in goldfish.

Morphometric studies on the testes of rats treated neonatally with oestrogen and subsequently with gonadotrophins and testosterone

The experiments involved male rats, which were given a single subcutaneous dose of 1 mg stilboestrol on the first day of life. Beginning on day 28, subgroups of the rats received either gonadotrophins or testosterone for 39 days. The weight of the testes, serum luteinizing hormone and testosterone levels were determined while sections of the testes were subjected to morphological analysis and morphometric measurements, based on computerized techniques. The results demonstrated that a single dose of oestrogen caused a reduction in the cross-sectional area of the seminiferous tubules and a reduction in the thickness of the seminiferous epithelium, accompanied by inhibition of spermatogenesis. The number of and area occupied by Leydig cells, as well as the size of their cell nuclei, were also diminished, and the levels of serum testosterone decreased by 73%. All the experimental animals manifested significantly increased serum luteinizing hormone levels. Stimulation with gonadotrophins markedly increased the number of Leydig cells, their size and the size of their cell nuclei. This was associated with significantly increased levels of serum testosterone. Under these conditions, the cross-sectional area of the seminiferous tubules and the thickness of seminiferous epithelium remained less than those in the untreated controls. Following stimulation with testosterone the pattern of the seminiferous tubules resembled that noted after stimulation with gonadotrophins; the number of Leydig cells was markedly reduced but the size of both the cells themselves and of their nuclei approached normal values.

Testicular Pathologic Changes and the Pituitary-Testicular Axis During Human Immunodeficiency Virus Infection

To chronicle pituitary-testicular axis dysfunction and its clinicopathologic features in homosexual men. Between 1984 and 1992, 84 homosexual men underwent longitudinal follow-up for 4 years. At entry into the study, 28 were seronegative and 56 were seropositive for human immunodeficiency virus (HIV). Although 40 subjects remained asymptomatic (nonprogressors), 16 had progression to acquired immunodeficiency syndrome (AIDS). Of those 16 patients with progression, 8 had AIDS within 2 years (early progressors) and 8 demonstrated AIDS within 4 years after enrollment (late progressors), and all died. The testes of five patients were examined at autopsy. The control group had similar follow-up. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and bioavailable testosterone (bio-T) were measured in stored sera collected at 2-year intervals. The last hormonal measurement was between 3 and 24 months before autopsy. Comparison was made between autopsied and nonautopsied patients with AIDS as well as between HIV nonprogressors and control seronegative men. The correlation between pathologic findings and hormonal status was examined by regression analysis. At baseline, testosterone, bio-T, LH, and FSH were not significantly different among all patients and subjects. During the study period, testosterone, bio-T, and serum gonadotropin levels remained unchanged in the seronegative homosexual men. In nonprogressors, serum FSH and LH concentrations remained unchanged, whereas testosterone and bio-T levels decreased significantly during this 4-year period. After progression to AIDS (in both groups of progressors), the serum FSH and LH levels were higher and the serum testosterone and bio-T were lower in comparison with values in the seronegative men. In late progressors to AIDS, FSH and LH increased, whereas serum testosterone and bio-T decreased significantly from baseline. All five patients with AIDS on whom autopsy was done had boundary wall thickening of the seminiferous tubules and decreased spermatogenesis. No significant differences were found in serum testosterone, bio-T, and LH between those in whom autopsy was or was not done; however, FSH was significantly higher in the autopsied cases. The serum testosterone and bio-T levels were negatively correlated with the interstitial inflammation. A significant correlation was also observed between change of bio-T and weight loss. We conclude that dysfunction of the pituitary-gonadal axis is common in HIV-infected men. All patients in whom autopsy was done because of AIDS-related diseases had been hypogonadal 3 to 24 months before death. Decreased spermatogenesis, subacute interstitial inflammation, or both were seen at autopsy of patients with AIDS. Pathologic damage to the testes during AIDS was associated with decreased testosterone and bio-T as well as increased serum gonadotropin levels. In a substantial proportion of men with progression to AIDS, compensated hypogonadism (normal serum testosterone and increased serum LH levels) preceded the development of low serum testosterone level.

The Correlation of Serum Luteinizing Hormone Levels with the Induction of Leydig Cell Tumors in Rats by Oxolinic Acid

Studies were performed to examine the mechanism by which testicular Leydig cell tumors are induced in rats by administration of the antimicrobial agent oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid). In these studies, the effects of oxolinic acid on serum levels of luteinizing hormone (LH), testosterone, and prolactin and the binding of testosterone to prostatic androgen receptors were examined. In a long-term hormonal study, male Wistar rats were fed a diet containing oxolinic acid at 0, 100, 1000, or 3000 ppm for 104 weeks. A statistically significant increase in serum LH levels was observed at 1000 and 3000 ppm, but no dose of oxolinic acid had a significant effect on serum testosterone levels. Serum LH levels were no longer elevated above control levels within 2 weeks of cessation of the administration of oxolinic acid. Oxolinic acid was found to have no effect on the rate of clearance of exogenous LH from the circulation. Serum prolactin levels were decreased by the administration of oxolinic acid. The increase in serum LH induced by oxolinic acid was completely blocked by the intraperitoneal injection of the dopamine antagonist haloperidol (2 mg/kg). In addition, no significant affinity of oxolinic acid for androgen receptors was found in an in vitro study. These findings suggest that: (1) oxolinic acid induces Leydig cell tumors in rats by chronically stimulating the release of LH from the pituitary, (2) the mechanism of stimulating the release of LH involves facilitation of the dopaminergic systems in the hypothalamus-pituitary axis, and (3) oxolinic acid has no effect on androgen-mediated feedback inhibition.

Leydig Cell Hyperplasia and Adenomas in Mice Treated with Finasteride, a 5α-Reductase Inhibitor: A Possible Mechanism

Leydig Cell Hyperplasia and Adenomas in Mice Treated with Finasteride, a 5α-Reductase Inhibitor: A Possible Mechanism. Prahalada, S., Majka, J. A., Soper, K. A., Nett, T. M., Bagdon, W. J., Peter, C. P, Burek, J. D., MacDonald, J. S., and van Zwieten, M. J. (1994). Fundam. Appl. Toxicol. 22, 211-219.Finasteride is a selective inhibitor of the enzyme 5α-reductase which is responsible for the conversion of testosterone (T) to dihydrotestosterone (DHT). Finasteride is indicated for the treatment of benign prostatic hyperplasia in man (∼ 0.1 mg/kg/day). The effect of long-term treatment was studied in mice given high doses (2.5, 25, and 250 mg/kg/day) of finasteride for 83 weeks. In finasteride-treated mice, increased incidences of testicular Leydig cell hyperplasia (52% compared to 24% in control group) at doses equal to or greater than 25 mg/kg/day and Leydig cell adenomas (32% compared to 0.5% in control group) at 250 mg/kg/day were observed. There were no drug-related effects on the seminiferous tubules. Since luteinizing hormone (LH) is a trophic hormone for Leydig cells, short-term studies (5 to 14 weeks) were clone to investigate the relationship between Leydig cell hyperplasia and serum LH levels in finasteride-treated mice. In these studies, there was a positive correlation between the drug-related increased incidence of Leydig cell hyperplasia and a statistically significant (p ⩽ 0.05) increase in serum LH levels in finasteride-treated (250 mg/kg/day) mice. Furthermore, studies in castrated male mice showed that the suppression of serum LH levels by T is reversible by inhibition of conversion of T to DHT with finasteride (250 mg/kg/day), supporting the hypothesis that DHT is involved in the regulation of LH release in mice. The data presented support the conclusion that the effects of finasteride on Leydig cells appear to be secondary to increased serum LH levels and that they occur only at very high doses when compared to the therapeutic dose (approximately 0.1 mg/kg/day) in man.

Basal Luteinizing Hormone and Follicle-Stimulating Hormone Release Rates as a Function of Time after Castration in Female and Male Rats

We investigated the potential importance of the basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release rates in causing the acute and chronic elevations in serum FSH and LH concentrations which occur after ovariectomy (OVX) and orchidectomy (ORCH) of rats. Diestrous day 1 female and male rats were decapitated or castrated and killed 2, 4 or 8 h or 1, 2, 7, 21 or 35 days later. In females, the weight of the anterior pituitary gland (APG) did not change. Serum FSH rose within 4 h and then progressively higher until 35 days after OVX. These increases were paralleled nearly perfectly with increases in APG FSH concentration which was first elevated at 1 day after OVX and in the basal FSH release rate (measured in vitro) which was first elevated at 4 h after OVX. Serum LH levels rose by 7 days after OVX and then more dramatically thereafter. These increases were associated with increased APG LH concentrations. The pronounced increases in serum LH levels between 7 and 35 days after OVX were associated with marked increases in the basal LH release rate. In males, APG weight was increased at 21 and 35 days after ORCH. Serum FSH levels were elevated at 1 day after ORCH and continued to rise until 21 days after ORCH. APG FSH concentration was decreased at 2 and 7 days and increased at 35 days after ORCH. The basal FSH release rate per milligram APG did not change significantly after ORCH. Serum LH levels were elevated at 8 h after ORCH. They rose further by 1 day and then further between 7 and 21 days after ORCH. APG LH concentration and the basal LH release rate per milligram APG were elevated at 21 and 35 days after ORCH. The results suggest that changes in basal FSH and LH release are (1) involved to a major extent in causing the post-OVX rise in serum FSH concentration during the first 5 weeks after OVX and in serum LH concentration between 7 and 35 days after OVX, (2) not involved in causing the post-ORCH rises in serum FSH and LH concentrations during the 1 week after ORCH, and (3) involved to some extent in causing the elevations in serum FSH and LH concentrations observed at 3 and 5 weeks after ORCH. The results also indicate that (1) increases in the basal gonadotropin release rates per milligram APG after castration may be coupled in some way with increased synthesis of gonadotropin, and (2) increases in the basal LH release rate per milligram APG can occur independently of an increase in the basal FSH release rate per milligram APG.

Interactions Between Opioid Peptides and Adrenaline-Containing Neurons Modulate Luteinizing Hormone Secretion in Male Rats

Abstract There is increasing evidence that the opioid inhibition of luteinizing hormone (LH) secretion is mediated, at least in part, by catecholaminergic mechanisms. This study determined the effects of selective manipulation of noradrenergic and adrenergic systems on the ability of opiate receptor blockade to induce the release of LH in adult male rats. Selective depletion of hypothalamic noradrenaline levels by 80% following 6-hydroxydopamine infusions into the central tegmental tract did not alter the 2- to 3-fold increase in serum LH levels following opiate receptor blockade with naloxone (2.5 mg/kg). In contrast, both selective depletion of hypothalamic adrenaline by prior treatment with the phenylethanolamine N-methyltransferase inhibitor, LY134046 (2 x 50 mg/kg) and non-selective depletion of all three catecholamines with alpha-methyl-p-tyrosine (250 mg/kg), abolished the naloxone-induced increase in LH. These results suggest that the inhibition of LH secretion by endogenous opioid peptides is influenced by catecholaminergic neurotransmission and further support the view that adrenaline rather than noradrenaline or dopamine is of importance in this context.

Immunization of Rams against Human Recombinant Inhibin α-Subunit Delays, Augments, and Extends Season-Related Increase in Blood Gonadotropin Levels1

Adult Suffolk rams were immunized four times against the human recombinant inhibin alpha-subunit over a period of 80 days. Blood samples were collected at weekly intervals and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were determined by radioimmunoassay procedures. The results show that season-related elevations of gonadotropin levels in immunized rams was delayed by 1-2 wk and, in these animals, it was more pronounced and extended than in vehicle-treated controls. Peaks of circulating testosterone were higher in control rams than in immunized animals. The capacity of the antisera to bind 125I-labeled inhibin alpha-subunit increased significantly in each immunized animal within 30 days of treatment, even though neutralizing antibodies were detected with a rat pituitary cell culture bioassay in only one of the four immunized rams. Epididymal sperm reserves tended to be greater in immunized than in control animals. These results show that inhibin controls the release of FSH during the breeding season, thereby regulating spermatogenic activity; it may also exert its effect on testicular function by a local effect on Leydig cells, as evidenced by changes in serum testosterone profiles and increased serum LH levels in rams immunized against the inhibin alpha-subunit.

Enhanced luteinizing hormone release by luteinizing hormone-releasing hormone in incubating female turkeys (Meleagris gallopavo).

To determine what role pituitary responsiveness plays in the suppression of gonadotropin level during incubation in the turkey, the ability of the pituitary to release luteinizing hormone (LH) in response to luteinizing hormone-releasing hormone (LHRH) was compared in incubating, laying, and photorefractory birds. In all three groups, the i.m. injection of LHRH (4 micrograms/kg) increased serum LH levels; however, the LH response was markedly enhanced in the incubating turkeys as compared with the laying (6.6-fold increase over preinjection levels vs. 1.9-fold; p less than 0.05) or the photorefractory birds (9.7-fold vs. 3.1-fold; p less than 0.05). The LHRH-induced LH release was also determined in turkeys as they shifted from the laying to the incubating phase of the reproductive cycle. This response increased (p less than 0.05) in magnitude as the birds started to incubate. The high prolactin level of incubating turkeys does not have a depressing effect on LHRH-stimulated LH release; thus, impaired LH response to LHRH is not a mechanism involved in the diminished gonadotropin secretion of incubating turkeys.

Nicotine-induced increases in brain luteinizing hormone releasing hormone-like immunoreactivity and in serum luteinizing hormone levels of the male rat

By means of radioimmunoassay procedures luteinizing hormone releasing hormone (LHRH)-, Met-enkephalin- and somatostatin-like immunoreactivities have been measured in discrete hypothalamic and preoptic nuclei as well as serum luteinizing hormone (LH) levels. Nicotine (2 mg/kg, i.p.) produced after 5 min a significant and selective increase in LHRH-like immunoreactivity in the median eminence and in the medial preoptic nucleus, associated with increases in serum LH levels but without any changes in Met-enkephalin and somatostatin-like immunoreactivities in the median eminence. The results indicate that the nicotine-induced activation of LHRH-immunoreactive neurons involves an enhanced processing of the precursor peptide to LHRH.