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Biomedical subjects

F C Wu

Publications and source records attributed to F C Wu.

At least 73 records · Page 4Linked to original sources

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I: Plasma luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, and inhibin concentrations.

Sex-steroid based male contraceptive regimes induce azoospermia in only 40-70% of Caucasian men. The reason(s) why the remainder maintains a low level of spermatogenesis (oligozoospermia) despite gonadotrophin suppression is unclear. In order to improve our understanding of this phenomenon, we examined the changes in sperm density and plasma LH, FSH, testosterone (T), oestradiol (E2), and inhibin (IN) in 28 normal men who received 200 mg testosterone enanthate (TE) im weekly during a male contraceptive efficacy trial. Gonadotrophins were measured by an ultrasensitive time-resolved immunofluorometric assay (DELFIA) with a sensitivity of 0.04 U/L, to determine the adequacy of suppression. Seventeen of the 28 men achieved azoospermia; the other 11 remained oligozoospermic (sperm density 3.3-4.7 x 10(6)/mL) after 6 months of TE exposure. Azoospermic subjects displayed a more rapid decline in sperm density, a significant difference being apparent by 5 weeks after starting TE. During TE treatment, both LH and FSH were consistently suppressed to below the limits of detection, whereas there was a 2.5-fold rise in T and E2 with a similar decrease in IN. There were no consistent differences in any of these hormone concentrations between the azoospermic and oligozoospermic groups. Recovery of sperm density to baseline levels or above 20 x 10(6)/mL was significantly slower in the azoospermic group. During the recovery phase, the azoospermic men exhibited significantly higher LH and FSH levels compared to baseline and to the oligozoospermic subjects even though no differences in circulating T, E2, or IN were observed. We conclude that incomplete gonadotrophin suppression or differences in sex steroid or inhibin levels are unlikely to be responsible for the maintenance of minor degrees of spermatogenesis in some men during TE administration. The rebound rise in gonadotrophins in azoospermic but not oligozoospermic responders during recovery may reflect a more profound degree of spermatogenic suppression in the former group.

Adult↗

Regulation of caulimovirus gene expression and the involvement of cis-acting elements on both viral transcripts.

In a further analysis of gene regulation of figwort mosaic virus (FMV), a caulimovirus, we studied transient gene expression with modified viral genomes in Nicotiana edwardsonii cell suspension protoplasts. The results demonstrated that the presence of the promoter for the full-length RNA interferes with expression from the separate downstream promoter for gene VI. In addition, expression of gene VI was inhibited by cis-acting sequences within gene VI itself. Both inhibitory effects could be partially relieved by coelectroporation with a plasmid that produces gene VI protein, demonstrating that expression of gene VI is transactivated by its own product. Subsequent expression studies with partially redundant FMV plasmids containing a reporter gene in frame with gene IV showed that efficient transactivation of CAT expression relies on a cis-acting element inside the downstream gene VI. Insertions of a transcriptional terminator upstream of the cis-acting element for premature termination of transcription showed that the cis-acting region is not a DNA element but is active only as a feature of the RNA transcript. We conclude that the cis-acting element, together with the transacting gene VI product, enhances expression of all major genes, including gene VI, from the polycistronic mRNA and the separate mRNA for gene VI.

Enhancer Elements, Genetic↗

Testicular steroidogenesis and androgen use and abuse.

The possibility of widespread use of androgens in the normal male population for the promotion of growth, sexual dysfunction, contraception, osteoporosis and ageing and large scale abuse by athletes have propelled androgen replacement out of the narrow confines of male hypogonadism and highlighted the many gaps in our knowledge. There is now a new appreciation of the much wider aetiological, therapeutic, preventative and public health implications surrounding the clinical use of androgens. To realize the many potential health benefits through manipulations of the androgen milieu of normal men, basic and clinical investigations into a number of key unresolved issues are urgently required. There is a need to understand the molecular mechanisms underlying the differential roles of testosterone, DHT and oestradiol in various androgen-responsive target tissues especially with reference to the pathogenesis of prostatic hyperplasia or carcinoma. It is also necessary to define the dose-response relationships of the action of androgens on spermatogenesis (and basis for inter-ethnic differences), sexual and aggressive behaviour and bone mineral turnover over a wide dose range. Clinically, it is important to systematically assess whether there is any increased risk for cardiovascular and prostatic diseases in androgen replacement and the risk-benefit issues concerning androgen therapy in aged men. Development of androgens with high therapeutic indices, long half-lives, zero-order release kinetics and perhaps selective target tissue specificity through modification to the steroid structure can further optimize future modalities of androgen therapy.

Anabolic Agents↗

Point mutations detected in the androgen receptor gene of three men with partial androgen insensitivity syndrome.

OBJECTIVE: Determine the sequence of the androgen receptor gene in men with impaired responsiveness to androgens in order to identify the molecular basis of their under-virilization. DESIGN: Blood samples were used as the source of genomic DNA. Portions of the androgen receptor gene were amplified by polymerase chain reaction and sequenced. PATIENTS: Samples were obtained from three patients and five normal fertile controls. Patients were all 46 XY and were undervirilized with ambiguous external genitalia, gynaecomastia and infertility. MEASUREMENTS: Total cellular DNA was purified from peripheral blood leucocytes. Pairs of oligonucleotide primers designed to flank the individual exons of the androgen receptor gene were synthesized. The specific regions of the androgen receptor were amplified from the samples of cellular DNA by polymerase chain reaction. Amplified DNA was purified, sequenced and compared to the published sequence. RESULTS: In all three patients point mutations in the androgen receptor gene were detected but no defects were detected in samples from normal controls. In two of the patients, an identical single nucleotide change from G to T was detected. This nucleotide was within the codon for amino acid 866 and would change it from valine to leucine. Amino acid 866 is found within an area of the steroid binding domain thought to be involved in receptor dimerization. Within the repetitive sequence of exon I patient 1 had 21 glutamine residues and patient 2 had 25. In the third patient a single change of G to A would result in incorporation of lysine in place of a conserved arginine residue at position 607 within the second zinc finger of the DNA binding domain. The sequence of the androgen receptor gene of the mother of the third patient revealed her to be heterozygous for the same defect. CONCLUSION: Patients 1 and 2 are unrelated although they have an identical point mutation in their androgen receptor gene. A patient with complete androgen insensitivity syndrome has been reported to have a defect at the same position causing the amino acid substitution of methionine for valine. Therefore we confirm that the nature of the amino acid change in the peptide sequence of the androgen receptor as well as its location within the protein, can have a profound effect on the phenotypic severity of androgen resistance. Studies on mutated receptors from individuals with a wide range of degrees of androgen resistance may enable us to construct a map of the key amino acids in the different domains of the protein.

Adult↗

Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive.

To investigate the fertility of men who remain oligozoospermic despite sex steroid suppression, the in-vitro fertilizing capacity of residual spermatozoa was assessed in 30 men receiving intramuscular testosterone enanthate (TE). Spermatozoa were prepared by either Percoll or repetitive centrifugation/washing. Although the mean (+/- SEM) pretreatment zona-free hamster oocyte penetration (HOP) rates were similar (59.4 +/- 10.1 and 63.8 +/- 10.8%), following the induction of oligozoospermia the Percoll-prepared spermatozoa exhibited a penetration rate (26.9 +/- 10.2%) which was markedly greater than that obtained for sperm prepared by repetitive washing (0 +/- 0%). In addition, the partners of two men exhibiting a HOP test with Percoll-prepared spermatozoa, conceived despite a sperm concentration of 3 x 10(6) ml-1 and a negative HOP test with spermatozoa prepared by repetitive washing. These results suggest that Percoll preparation optimizes the assessment of in-vitro sperm function and that the fertility of men with TE-induced severe oligozoospermia is suppressed but not abolished.

Adult↗

The full-length transcript of a caulimovirus is a polycistronic mRNA whose genes are trans activated by the product of gene VI.

Gene expression of figwort mosaic virus (FMV), a caulimovirus, was investigated by electroporation of Nicotiana edwardsonii cell suspension protoplasts with cloned viral constructs in which a reporter gene was inserted at various positions on the genome. The results showed that the genome of FMV contains two promoters; one is used for the production of a full-length RNA and another initiates synthesis of a separate monocistronic RNA for gene VI. Evidence is provided that the full-length transcript, the probable template for reverse transcription, can serve as a polycistronic mRNA for translation of genes I through V and perhaps also gene VI. Expression of all the genes on the polycistronic mRNA is trans activated by the gene VI protein. Reporter gene expression appears most efficient when its start codon is in close proximity to the stop codon of the preceding gene, as for the native genes of caulimoviruses. We propose that the gene VI product enables expression of the polycistronic mRNA by promoting reinitiation of ribosomes to give translational coupling of individual genes.

Cells, Cultured↗

Oral testosterone undecanoate in the management of delayed puberty in boys: pharmacokinetics and effects on sexual maturation and growth.

Therapeutic induction of puberty using oral testosterone (T) undecanoate (TU) 40 mg daily was performed in 4 pubertal boys aged 12.7-17.1 yr with constitutional delayed puberty and/or short stature. Single-dose pharmacokinetics study was performed on matched plasma and saliva samples obtained half-hourly for 10 h after the first dose and then repeated 3 and 6 months later. Treatment was continued for 15-21 months. Peak plasma total T concentration was achieved at 255 +/- 51 (SEM) min after the first 40 mg dose of TU, 300 +/- 76 min at 3 months, and 293 +/- 103 min at 6 months, the levels remaining elevated above baseline for at least 8 h after a single oral dose. Total T levels were initially high (mean 13.0 +/- 2.5; peak 38.7 +/- 4.2 nmol/L) but dropped significantly at 3 months (mean 8.3 +/- 1.8; peak 23.6 +/- 5.6 nmol/L) and at 6 months (mean 9.2 +/- 1.6; peak 24.8 +/- 3.5 nmol/L) paralleled by a dramatic fall in sex hormone binding globulin (73.9 +/- 18.0 to 35.1 +/- 9.7 at 3 month and 29.2 +/- 6.0 nmol/L at 6 month). Mean concentrations of unbound and free T (non-sex hormone binding globulin-bound T, free T, and salivary T) were below the normal adult range and remained unchanged over the same period. Plasma dihydrotestosterone concentrations were elevated after the first dose (mean 5.4 +/- 1.3; peak 11.0 +/- 2.5 nmol/L), the extent of this rise being less after 6 months (mean 4.1 +/- 0.8; peak 7.1 +/- 1.1 nmol/L) as was the case with mean estradiol (51.5 +/- 8.9 to 38.1 +/- 3.7 pmol/L). Signs of virilization progressed to Tanner stage G3 PH2-3 with testicular volumes increasing to 3-4 mL at 12 months, and G4 PH4-5 with further testicular growth to 6-10 mL at 24 months. Height velocity rose from 3.2 +/- 0.3 cm/yr (pretreatment) to 7.2 +/- 1.0 cm/yr in the first year and was maintained at 7.3 +/- 0.4 cm/yr despite cessation of therapy during the second year. Bone age advanced by 1.1 +/- 0.1 yr at 12 months and a further 0.8 +/- 0.3 yr at 24 months. Predicted adult height remained unchanged. No side effects were observed. Our preliminary data suggest that oral TU is a well accepted, effective, and safe treatment for the initiation of male puberty without disproportionate skeletal maturation. Continued pubertal advance was evident after cessation of treatment in all patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

The effects of exogenous testosterone on sexuality and mood of normal men.

The effects of supraphysiological levels of testosterone, used for male contraception, on sexual behavior and mood were studied in a single-blind, placebo-controlled manner in a group of 31 normal men. After 4 weeks of baseline observations, the men were randomized into two groups: one group received 200 mg testosterone enanthate (TE) weekly by im injection for 8 weeks (Testosterone Only group), the other received placebo injections once weekly for the first 4 weeks followed by TE 200 mg weekly for the following 4 weeks (Placebo/Testosterone group). The testosterone administration increased trough plasma testosterone levels by 80%, compatible with peak testosterone levels 400-500% above baseline. Various aspects of sexuality were assessed using sexuality experience scales (SES) questionnaires at the end of each 4-week period while sexual activity and mood states were recorded by daily dairies and self-rating scales. In both groups there was a significant increase in scores in the Psychosexual Stimulation Scale of the SES (i.e. SES 2) following testosterone administration, but not with placebo. There were no changes in SES 3, which measures aspects of sexual interaction with the partner. In both groups there were no changes in frequency of sexual intercourse, masturbation, or penile erection on waking nor in any of the moods reported. The Placebo/Testosterone group showed an increase in self-reported interest in sex during testosterone treatment but not with placebo. The SES 2 results suggest that sexual awareness and arousability can be increased by supraphysiological levels of testosterone. However, these changes are not reflected in modifications of overt sexual behavior, which in eugonadal men may be more determined by sexual relationship factors. This contrasts with hypogonadal men, in whom testosterone replacement clearly stimulates sexual behavior. There was no evidence to suggest an alteration in any of the mood states studied, in particular those associated with increased aggression. We conclude that supraphysiological levels of testosterone maintained for up to 2 months can promote some aspects of sexual arousability without stimulating sexual activity in eugonadal men within stable heterosexual relationships. Raising testosterone does not increase self-reported ratings of aggressive feelings.

Adult↗

Differential contribution of leucocytes and spermatozoa to the generation of reactive oxygen species in the ejaculates of oligozoospermic patients and fertile donors.

Cells isolated from the ejaculates of a high proportion of patients exhibiting oligozoospermia are characterized by generation rates of reactive oxygen species that considerably exceed those obtained for the normal fertile population. The purpose of this study was to resolve the cellular source of this enhanced activity. Semen samples from a cohort of oligozoospermic patients and a group of fertile controls were fractionated on discontinuous Percoll gradients to generate three cell populations (0, 50 and 100%) of differing density. For each fraction, both the steady-state and the phorbol-ester-induced chemiluminescent signals were significantly (P less than 0.001) greater for the oligozoospermic samples than for the fertile controls. In the fertile donors, leucocytes comprised the major source of reactive oxygen species, particularly in the low-density Percoll fractions; in oligozoospermic patients, however, spermatozoa were identified as a second major source of reactive oxygen species. Particularly striking was an intense phorbol-ester-induced chemiluminescent signal generated by oligozoospermic spermatozoa, purified by passage through isotonic Percoll and free of leucocyte contamination, which was 167 times greater than the median signal generated by the corresponding fraction from the fertile controls (P less than 0.001). These results emphasize the importance of spermatozoa as a major source of reactive oxygen species in oligozoospermia and have implications for the diagnosis and treatment of this condition, as well as for the design of appropriate diagnostic strategies.

Cell Separation↗

Requirement of gene VII in cis for the expression of downstream genes on the major transcript of figwort mosaic virus.

The six major conserved genes of figwort mosaic virus (FMV), a caulimovirus, appear in tandem array on an RNA transcript that spans the entire viral genome. Gene VI, the only cistron that appears as a separate subgenomic RNA, has been reported to transactivate the expression of downstream genes of the full-length transcript. This transcript has a long 5'-leader of about 600 nucleotides followed by a small nonconserved region (gene VII), a smaller intergenic region (57 nucleotides), and the major conserved genes in a closely spaced array. In our present experiments we have constructed expression units containing the promoter for the full-length transcript followed by the 5' leader region, gene VII, and a reporter gene. These have been tested for expression with and without gene VI as a separate plasmid by electroporation into plant protoplasts. A series of these expression units containing truncated versions of the 5' leader region placed upstream of a reporter gene (CAT) showed that gene VI transactivation occurred only when gene VII sequences were present in cis between the leader region and the reporter gene. In addition, a more complete version of the FMV genome containing the reporter gene further downstream (in viral gene IV) showed CAT expression only when gene VII sequences were present in an upstream position. A similar construct failed to express CAT activity when gene VII was absent.

Chloramphenicol O-Acetyltransferase↗

A naturally occurring deletion mutant of figwort mosaic virus (caulimovirus) is generated by RNA splicing.

A naturally occurring deletion mutant is observed in plants infected with figwort mosaic virus (FMV), a caulimovirus. The encapsidated mutant genome is formed spontaneously in association with two different strains of FMV in four host plant species. The mutant also appears when cloned wild-type viral DNA is used as the inoculum. The deletion mutant alone is not infectious and it appears unable to replicate after its formation, even in the presence of wild-type virus. The gene for chloramphenicol acetyltransferase was inserted at different positions in the deletion mutant genome, and subsequent transient assays showed that gene expression of the mutant occurs despite the deletion. Sequence analyses of the mutant genome revealed a deletion of 1237-bp segment encompassing a major portion of the coat protein gene and the 5' end of the downstream reverse transcriptase gene. This deletion is associated with consensus signals for RNA splicing including the conserved 5' and 3' splice sites plus surrounding sequences, putative branch point(s) for lariat formation, and an extremely high adenosine content (41%) of the removed fragment. This suggests that splicing of the FMV full-length transcript has occurred prior to reverse transcription and this accounts for the presence and accumulation of encapsidated DNAs with the same deletion.

Base Sequence↗

Immunosuppression by seminal plasma from fertile and infertile men: inhibition of natural killer cell function correlates with seminal PG concentration.

Human seminal plasma has uniquely high concentrations of PGE and 19-hydroxy PGE but the function of these PGs has not been elucidated. PGs of the E series have been shown to be paracrine and autocrine regulators of the function of immune cells and high levels of PGE have been shown consistently to suppress function in such cells. Human seminal plasma has a potent immunosuppressive effect and evidence is accumulating that this is largely due to PG components. In this study the effects of human seminal plasma on the killing activity of natural killer (NK) cells as judged by 51Cr release from K562 cells have been studied in groups of fertile and infertile men. Although there was no significant difference in the PGE, 19-hydroxy PGE or the NK cell inhibitory activity in the two groups, the inhibition of NK cell activity was closely correlated with the PGE and the 19-OH PGE content of the seminal plasma in the fertile group. This finding is further evidence that the major contribution to the immunosuppressive properties of human semen is provide by the high concentration of PGs of the E series in this fluid.

Alprostadil↗

Prospective analysis of sperm-oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility.

We have undertaken a prospective analysis of the diagnostic significance of three different criteria of human sperm function including the conventional semen profile, measurements of hamster-oocyte fusion, and determinations of reactive oxygen species generation in 139 couples. The latter, who were characterized by a lack of detectable abnormalities in the female partner, were followed up for a maximum of 4 years to determine the incidence of spontaneous pregnancy in the absence of therapeutic intervention. Assessments of monthly fecundity with life table analysis techniques revealed a highly significant, positive relationship between fertility and hamster-oocyte fusion rates that were measured in the presence of the ionophore, A23187. Conversely, reactive oxygen species generation was shown to be negatively associated with both the outcome of the sperm-oocyte fusion assay and fertility in vivo. The clinical significance of these diagnostic techniques was emphasized by the fact that within the same data set, the conventional semen profile was of no significant diagnostic value.

Animals↗

Thiamin requirement of juvenile shrimp (Penaeus monodon).

In a 9-wk feeding trial, juvenile shrimp (Penaeus monodon) were fed semipurified diets containing seven levels (0, 20, 40, 60, 80, 160 and 320 mg/kg diet) of supplemental thiamin hydrochloride. The dietary thiamin level required for optimal growth in P. monodon was found to be approximately 14 mg/kg diet based on hemolymph (blood) thiamin analysis. The minimum dietary thiamin level that produced substantial shrimp growth was approximately 13 mg/kg diet. Shrimp fed unsupplemented diets (thiamin content of 0.12 mg/kg diet) did not demonstrate specific deficiency signs, except those universal signs such as retarded growth, poor food conversion and low survival rates.

Animals↗

Patterns of pulsatile luteinizing hormone and follicle-stimulating hormone secretion in prepubertal (midchildhood) boys and girls and patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome): a study using an ultrasensitive time-resolved immunofluorometric assay.

To study the ontogeny of spontaneous pulsatile LH and FSH secretion before the onset of puberty, plasma LH and FSH were measured by an ultrasensitive time-resolved immunoflurometric assay in 16 boys and 6 girls, aged 6.5 +/- 0.2 yr (+/- SEM; range, 4.4-8.0) with short stature. Eight male patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome), aged 24.1 +/- 3.4 yr, were also investigated. Blood samples were withdrawn at 10- to 20-min intervals for 12 h from 2000-0800 h. Pituitary responsiveness was assessed by a standard iv LHRH challenge test. LH and/or FSH pulses were detectable in all but two prepubertal subjects. In boys, low amplitude LH (0.16 +/- 0.06 U/L) and FSH (0.19 +/- 0.03 U/L) pulses were detectable at mean frequencies of 2.19 +/- 0.37 and 2.13 +/- 0.46 pulses/12 h, respectively. In girls, low amplitude LH (0.29 +/- 0.18 U/L) pulses, but higher (P less than 0.05 compared to boys) amplitude FSH (1.62 +/- 1.05 U/L) pulses were observed at frequencies of 1.71 +/- 0.56 and 1.67 +/- 0.53 pulses/12 h, respectively. Mean FSH in prepubertal girls (1.95 +/- 0.88 U/L) was significantly (P less than 0.05) higher than that in boys (0.46 +/- 0.07 U/L), but mean LH was not different at 0.17 +/- 0.07 and 0.10 +/- 0.03 U/L, respectively. Patients with Kallmann's syndrome had mean LH and FSH levels indistinguishable from those of prepubertal boys. Nocturnal augmentation of pulsatile LH or FSH secretion was observed in 74% of children (71% in girls and 75% in boys), but in none of the eight patients with Kallmann's syndrome. A close temporal association was observed between sleep onset and the appearance of nocturnal pulsatile gonadotropin secretion. The FSH response to exogenous LHRH in prepubertal girls was significantly greater than that in patients with Kallmann's syndrome and prepubertal boys, but LH responses were not different. Our results show that pulsatile LH and FSH secretion occurs in the majority of boys and girls in midchildhood, with a robust association with nocturnal sleep onset. Between the ages of 4-8 yr, these low amplitude and low frequency pulses are unable to activate gonadal function. The regulation of FSH secretion in prepubertal girls appears to be different from that in prepubertal boys.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

Effects of decreasing exogenous GnRH pulse frequency on FSH and inhibin secretion in men with idiopathic hypogonadotropic hypogonadism.

The potential importance of GnRH pulse frequency modulation and steroid or inhibin negative feedback in the selective control of pituitary FSH secretion was investigated in 5 adult men with idiopathic hypogonadotropic hypogonadism in whom plasma testosterone has been previously normalized by pulsatile GnRH therapy. The effects of decreasing frequency of pulsatile iv GnRH administration from 2- to 4-hourly for 7 days were examined at constant GnRH bolus dose or constant daily dose and also with interrupted gonadal steroid feedback using a combination of an anti-androgen (flutamide 250 mg t.i.d.) and an aromatase inhibitor (aminogluthetimide 125 mg b.d.) orally for a further 7 days. Slowing GnRH pulse frequency from 2- to 4-hourly did not alter mean plasma FSH at constant bolus dose or constant total daily doses of GnRH. In two subjects with subnormal but not in another two with normal testicular volumes, FSH rise was observed when the 4-hourly GnRH pulse frequency was combined with the interruption of steroid feedback. These results are not compatible with a major role for GnRH pulse frequency modulation in the regulation of pituitary FSH secretion in the presence of normal gonadal steroid feedback. Irrespective of FSH concentrations, plasma inhibin immunoactivity did not change significantly with the alteration in GnRH pulse frequency. The role of inhibin in the control of FSH therefore remains undefined in men.

Adult↗

Effect of depot medroxyprogesterone acetate and testosterone oenanthate on serum lipoproteins in man.

Ten normal men were given three monthly intramuscular injections of 200mg of depot medroxyprogesterone acetate (DMPA) and 250mg of testosterone oenanthate (TE) as part of a male contraceptive trial. During the three months of treatment, serum high density lipoprotein cholesterol (HDL-C) and the HDL-C:LDL-C (low density lipoprotein cholesterol) ratio were significantly depressed compared to baseline. Although the long-term effect of this alteration in lipoprotein cholesterol metabolism in normolipidaemic men is currently uncertain, these results suggest that the potential cardiovascular risks of progestagen-containing regimens for male contraception will have to be seriously considered.

Adult↗

Patterns of pulsatile luteinizing hormone secretion before and during the onset of puberty in boys: a study using an immunoradiometric assay.

To study spontaneous pulsatile LHRH/LH secretion around the onset of puberty, nocturnal plasma LH was measured by means of a highly sensitive immunoradiometric assay in 30 boys (aged 5.6-16.8 yr) investigated for potential problems with growth and/or development. Blood was withdrawn at 10- to 20-min intervals from 2000-0800 h. Pulse analysis was accomplished by a computerized peak detection algorithm. Pituitary and gonadal responsiveness was assessed by a standard exogenous LHRH challenge and testosterone. Subsequent clinical progress was monitored for a mean duration of 2.08 +/- 0.16 yr and used as the basis for classifying patients retrospectively into three groups: 1) prepubertal (n = 14), 2) peripubertal (n = 11), and 3) pubertal (n = 5). LH pulses were undetectable in 9 and present in 5 prepubertal subjects, the youngest of whom was aged 7.3 yr. In peripubertal and pubertal individuals, 2-7 LH pulses/12 h were detectable. LH pulses were detectable before sleep by midpuberty (Tanner stage 3). There was a highly significant (P less than 0.0001) increase in LH/LHRH pulse frequency from 0.93 +/- 0.38 to 4.55 +/- 0.43/12 h (mean +/- SEM) between the prepubertal and peripubertal groups and a further increase to 6.20 +/- 0.37/12 h in the pubertal group. LH pulse amplitude remained under 1.0 U/L in both the prepubertal and peripubertal groups and only increased significantly to 2.02 +/- 0.17 U/L in pubertal boys. Response to LHRH increased significantly between the prepubertal (2.47 +/- 0.49 U/L) and peripubertal (6.53 +/- 2.02 U/L) patients. T increased significantly at each stage, with the greatest rise between the peripubertal and pubertal stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗