Increased Plasma Follicle-stimulating Hormone Research Articles

A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women.

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which can potentially be fatal due to exsanguination following rupture. Although AAA is less prevalent in women, women with AAA have a more severe AAA progression compared to men as reflected by enhanced aneurysm growth rates and a higher rupture risk. Women are diagnosed with AAA at an older age than men, and in line with increased osteoporosis and cardiovascular events, the delayed AAA onset has been attributed to the reduction of the protective effect of oestrogens during the menopausal transition. However, new insights have shown that a high follicle stimulating hormone (FSH) level during menopause may also play a key role in those diseases. In this report we hypothesize that FSH may aggravate AAA development and progression in postmenopausal women via a direct and/or indirect role, promoting aorta pathology. Since FSH receptors (FSHR) are reported on many other cell types than granulosa cells in the ovaries, it is feasible that FSH stimulation of FSHR-bearing cells such as aortic endothelial cells or inflammatory cells, could promote AAA formation directly. Indirectly, AAA progression may be influenced by an FSH-mediated increase in osteoporosis, which is associated with aortic calcification. Also, an FSH-mediated decrease in cholesterol uptake by the liver and an increase in cholesterol biosynthesis will increase the cholesterol level in the circulation, and subsequently promote aortic atherosclerosis and inflammation. Lastly, FSH-induced adipogenesis may lead to obesity-mediated dysfunction of the microvasculature of the aorta and/or modulation of the periaortic adipose tissue. Thus the long term increased plasma FSH levels during the menopausal transition may contribute to enhanced AAA disease in menopausal women and could be a potential novel target for treatment to lower AAA-related events in women.

Molecular characterization of gonadotropin subunits (fshβ, lhβ and cgα) of largemouth bass ( micropterus salmoides ) and their expression in response to luteinizing hormone‐releasing hormone analogue and dopamine antagonists

Gonadotropins (GtHs), including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are important hormones involved in gametogenesis, gonadal steroidogenesis, and maturation. In this study, GtH subunits (FSHβ, LHβ and CGα) of largemouth bass (Micropterus salmoides) were cloned and characterized, and their regulation by luteinizing hormone-releasing hormone analog (LHRHa2) and dopamine antagonist (DOM) treatment in vivo was investigated. The full-length cDNA sequences of FSHβ, LHβ, and CGα were 683, 576, and 685bp, encoding 120, 152, and 132 amino acids, respectively. The deduced amino acid sequence analysis revealed that GtH subunits contain conserved cysteine residues and potential N-linked glycosylation sites and showed high homology with the corresponding subunit sequences from other Perciformes by phylogenetic analysis. In the primary growth cortical alveoli stage of largemouth bass, the three GtH subunits were highly expressed in the pituitary, brain and ovary, but weakly in other tissues. After LHRHa2 and DOM injection, mRNA levels of FSHβ, LHβ, and CGα in the pituitary were significantly increased at 12 or 24 hr (p <.05), but significantly decreased at 48 hr; plasma FSH and LH levels showed a consistent trend. Histological analysis classified ovaries from LHRHa2- and DOM-treated fish into the early oocyte maturation stage and late vitellogenesis stage, while those from the control group fish were classified into the early vitellogenesis stage. These results suggested that both LHRHa2 and DOM stimulated GtH subunit expression, increased plasma FSH and LH and accelerated ovary development of largemouth bass, providing a framework for a better understanding of the mechanisms of hormone-mediated reproduction control in teleosts.

Development of specific enzyme-linked immunosorbent assay for yellowtail kingfish (Seriola lalandi) follicle stimulating hormone using recombinant gonadotropins

We developed a specific competitive enzyme-linked immunosorbent assay (ELISA) for yellowtail kingfish (Seriola lalandi) follicle stimulating hormone (FSH). We previously produced a full-length single chain recombinant yellowtail kingfish FSH using the Pichia pastoris expression system. We used the same method to produce the β subunit of the hormone, against which polyclonal antibodies were raised in rabbits. We first confirmed immunoreactivity of the polyclonal antibodies with the recombinant full length FSH and FSHβ as well as plasma and pituitary FSH of sexually immature and mature yellowtail kingfish by Western blot analysis. We then developed a precise and reproducible ELISA for yellowtail kingfish FSH and validated the assay in plasma and pituitary extracts. The intra- and inter-assay coefficients of variation was <2.2% and 10.2%, respectively. The sensitivity of the assay was 78 pg/ml. For further validation of the assay, we measured the plasma FSH in immature yellowtail kingfish treated with increasing doses (blank, 50, 100 and 150 µg/kg) of kisseptin2-10 peptide from a previous study. The dose response observed in treated females was not significant, however the increased plasma FSH levels coincided with the significantly higher estradiol levels we previously reported in the treated groups. We assessed the applicability of the assay in measuring circulating FSH in other species. We observed parallelism between the linearized FSH standard curve and displacement curves of serially diluted plasma from Atlantic bluefin tuna (Thunnus thynnus) and tilapia (Oreochromis niloticus). We also observed similar parallelism with full length recombinant giant grouper (Epinephelus lanceolatus) FSH. The ELISA we developed for yellowtail kingfish FSH will be useful in understanding the reproductive biology of the species as well as enhancing its aquaculture.

Brain thromboxane A2 via arachidonic acid cascade induces the hypothalamic-pituitary-gonadal axis activation in rats.

The current study was designed to determine the effect of centrally administrated arachidonic acid (AA) on plasma gonadotropin hormone-releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone level, and sperm parameters, and to show the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway in AA-induced hormonal and sperm parameter effects. Studies were performed in male Sprague-Dawley rats. A total of 150 or 300 μl/5 μl doses of AA were injected intracerebroventricularly (icv). AA significantly caused dose- and time-dependent increases in plasma FSH, LH and testosterone levels of animals, but not plasma GnRH level. AA also significantly increased sperm motility of the rats without change sperm number. Pretreated with ibuprofen, a nonselective COX inhibitor (250 μg/5 μl; icv), and furegrelate, a TXA2 synthesis inhibitor (250 μg/5 μl; icv), prevented AA-evoked increase in plasma FSH, LH and testosterone levels, and sperm motility. In conclusion, our findings show that centrally administered AA increases plasma FSH, LH and testosterone levels and sperm motility of conscious male rats. Moreover, according to our findings, central COX-TXA2 signaling pathway mediates these AA-induced effects.

Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal axis in male and female dogs before and after gonadectomy

GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study was to obtain more insight into the pituitary-gonadal axis in intact and neutered dogs and to establish reference values. Basal plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were increased significantly after gonadectomy in both bitches and male dogs. In both males and females ranges of the basal plasma FSH concentrations, before and after gonadectomy, did not overlap as opposed to the overlap in ranges of the basal plasma LH concentrations. Before gonadectomy basal plasma LH concentrations were lower and basal plasma FSH concentrations were higher in bitches than in male dogs. After gonadectomy these basal values did not differ significantly. GnRH administration before gonadectomy resulted in an increase in plasma LH and FSH concentrations in both genders. GnRH administration after gonadectomy produced an increase only in plasma LH concentrations in both genders, and a just significant increase in plasma FSH in castrated male dogs. GnRH administration before gonadectomy resulted in a significant increase in plasma testosterone concentration in both genders. In males ranges of basal and GnRH-stimulated plasma testosterone concentrations before and after gonadectomy did not overlap. Basal plasma estradiol concentrations were significantly higher in intact males than in castrated males and their ranges did not overlap. The basal estradiol concentrations in bitches before and after ovariectomy were not significantly different. At 120 min after GnRH administration, ranges of plasma estradiol concentration of intact and ovariectomized bitches no longer overlapped. In conclusion, basal plasma FSH concentration appears to be more reliable than basal plasma LH concentration for verification of neuter status in both male and female dogs. The basal plasma testosterone concentration appears to be reliable for verification of neuter status in male dogs. The plasma estradiol concentration at 120 min after GnRH administration can be used to discriminate between bitches with and without functional ovarian tissue.

PREDICTION OF SUCCESSFUL OUTCOME OF MICRODISSECTION TESTICULAR SPERM EXTRACTION IN MEN WITH IDIOPATHIC NONOBSTRUCTIVE AZOOSPERMIA

Microsurgical techniques in testicular sperm extraction can improve sperm retrieval in patients with nonobstructive azoospermia (NOA). However, spermatozoa retrieval rates have still been reported to be around 50% for patients with NOA. Thus, a reliable prediction method for successful outcome is needed to avoid unnecessary surgery. In this retrospective study we determined the diagnostic and predictive values of noninvasive parameters used in the treatment of patients with NOA. We analyzed 9 preoperative factors including patient age, testicular volume and endocrinological data of 100 patients with NOA using multivariate logistic modeling. Testicular spermatozoa were retrieved successfully in 41 of the 100 patients (41%). We found that the concentrations of follicle-stimulating hormone (FSH), total testosterone (TT) and inhibin B were considered the most influential preoperative factors. We developed a formula to calculate the probability of successful outcome, P = [1 + exp(5.201 - 0.048 x FSH - 0.449 x TT - 0.021 x inhibin B)](-1). Association of predicted probabilities and observed responses was 0.77. A predicted probability of more than 15.7% was found to be the best cutoff. Sensitivity was 71.0% and specificity was 71.4% as determined by receiver operating characteristic analysis. We concluded that our formula should be useful for doctors considering microdissection testicular sperm extraction for patients with NOA because our equation uses noninvasive parameters without a preoperative testicular biopsy, which is a relatively invasive examination.

Central and Peripheral Administration of Kisspeptin‐10 Stimulates the Hypothalamic‐Pituitary‐Gonadal Axis

Kisspeptin is the peptide product of the KiSS-1 gene and the endogenous agonist for the GPR54 receptor. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. We examined the effect of intracerebroventricular (i.c.v.) and peripheral administration of the active kisspeptin fragment, kisspeptin-10, on circulating gonadotrophins and total testosterone levels in adult male rats. The effect of kisspeptin-10 in vitro on the release of hypothalamic peptides from hypothalamic explants and gonadotrophins from anterior pituitary fragments was also determined. The i.c.v. administration of kisspeptin-10 dose-dependently increased plasma luteinizing hormone (LH) and increased plasma follicle stimulating hormone (FSH) and total testosterone at 60 min postinjection. In a separate study investigating the time course of this response, i.c.v. administered kisspeptin-10 (3 nmol) significantly increased plasma LH at 10, 20 and 60 min, FSH at 60 min and total testosterone at 20 and 60 min postinjection. Kisspeptin-10 stimulated the release of luteinizing hormone-releasing hormone (LHRH) from in vitro hypothalamic explants. Peripheral administration of kisspeptin-10 increased plasma LH, FSH and total testosterone. However, doses of 100-1000 nM kisspeptin-10 did not influence LH or FSH release from pituitary fragments in vitro. Kisspeptin therefore potently stimulates the hypothalamic-pituitary-gonadal axis. These effects are likely to be mediated via the hypothalamic LHRH system.

Cadmium effects on hypothalamic-pituitary-testicular axis in male rats.

This study analyzes cadmium effects at the hypothalamic-pituitary-testicular axis. Male rats were given cadmium during puberty or adulthood. Cadmium exposure through puberty increased norepinephrine content in all hypothalamic areas studied, but not in the median eminence. Metal exposure increased serotonin turnover in median eminence and the anterior hypothalamus, while decreased it in mediobasal hypothalamus. Also, decreased plasma levels of testosterone were found. Cadmium exposure during adulthood increased norepinephrine content in posterior hypothalamus and decreased the neuro-transmitter content in anterior and mediobasal hypothalamus. Decreased circulating levels of luteinizing hormone (LH) and testosterone and increased plasma follicle stimulating hormone (FSH) levels were also observed. Cadmium accumulated in all analyzed tissues. Various parameters showed age-dependent changes. These data suggest that cadmium globally effects hypothalamic-pituitary-testicular axis function by acting at the three levels analyzed and that an interaction between cadmium exposure and age emerge.

Regulatory Role of Inhibin in Follicle-Stimulating Hormone Secretion and Folliculogenesis in the Guinea Pig.

The effects of unilateral and bilateral ovariectomy and passive immunization against inhibin on follicle-stimulating hormone (FSH) secretions and follicular development in the guinea pig were investigated. Bilateral ovariectomy decreased plasma immunoreactive (ir-) inhibin rapidly and increased plasma FSH significantly. Unilateral ovariectomy decreased plasma ir-inhibin and increased plasma FSH temporarily, and doubled the number of ova released from the remaining ovary at the subsequent ovulation in guinea pigs. Injection of 1.0 ml inhibin antiserum significantly increased concentrations of plasma FSH at 6 hr onwards and the number of small follicles (100-200 microm in diameter) at 48 hr after the injection in guinea pigs bearing progesterone-containing implants. In vitro bioassay showed that inhibin antiserum could neutralize the suppression of ovarian homogenate on FSH secretion from cultured rat anterior pituitary cells. These results confirm the evidence that the ovary is the main source of inhibin secretion and both in vitro bioassay and passive immunization against inhibin show that the inhibin is a major regulator in the follicular development through FSH secretion in guinea pigs.

Contribution of endogenous inhibin to the decline of the secondary surge of follicle-stimulating hormone in the rat.

The involvement of inhibin in the decline of the secondary surge of follicle-stimulating hormone (FSH) was investigated in the rat. After ovariectomy or treatment with inhibin antiserum conducted at 2300 hours during pro-oestrus, plasma concentrations of FSH were maintained at high levels compared with control rats. However, plasma FSH started to decline at 0500 hours during oestrus in both the groups. The same treatments conducted during metoestrus markedly increased plasma FSH after 24 h (twofold compared with the treatments during pro-oestrus), suggesting that the treatments sufficiently depleted circulating inhibin. To examine whether the decline of plasma FSH occurred through a transcriptional mechanism or through a translational mechanism, FSH-beta mRNA expression and the pituitary concentration of FSH were measured. Neither ovariectomy nor inhibin immunization conducted during the night of pro-oestrus, affected the pituitary concentration of FSH after 24 h, whereas a noticeable increase was observed after the treatments conducted during metoestrus. In both stages, both ovariectomy and inhibin immunization significantly increased FSH-beta mRNA expression compared with control rats. In contrast with the pituitary concentration of FSH, the effect of inhibin immunization on FSH-beta mRNA expression was not different between the stages. The present data demonstrate the involvement of inhibin in the decline of the secondary surge of FSH, and suggest that a factor or factors other than inhibin may also be responsible for the fall in FSH. Changes in the pituitary concentration of FSH and FSH-beta mRNA expression suggest that post-transcriptional mechanisms may be involved in the suppression of FSH secretion during oestrus.

Synchronization of endogenous and exogenous FSH stimuli in controlled ovarian hyperstimulation (COH).

We have previously observed that exogenous oestradiol can delay the intercycle increase in plasma follicle stimulating hormone (FSH). The increase in plasma FSH that follows discontinuation of exogenous oestradiol peaks after 3 days. We have now studied the possibility of using exogenous oestradiol to synchronize the increase in endogenous FSH with the onset of human menopausal gonadotrophin (HMG) treatment in controlled ovarian hyperstimulation (COH). A total of 30 women aged 35.1+/-6.3 years (mean+/-SD) undergoing ovarian stimulation received 2 mg of oestradiol valerate twice daily starting on day 25 of the previous menstrual cycle until the first Tuesday following menses. Ovarian stimulation was initiated 3 days later. On the last day of oestradiol treatment, plasma oestradiol, FSH and luteinizing hormone (LH) (mean+/-SEM) were 566+/-53 (pmol/l), 3.8+/-0.4 (IU/l) and 5.5+/-0.8 (IU/l) respectively. After 3 days, the FSH and LH (mean+/-SEM) had increased to 6.7+/-0.7 and 6.9+/-0.7 (IU/l) respectively while oestradiol decreased to 251+/-29 (pmol/l). The mean number (+/-SEM) of HMG ampoules used was 25.1+/-2.7 and treatment lasted 11.3+/-0.9 days. Five women became pregnant for a pregnancy rate (ongoing) of 19 (15)%. If all women aged >40 years (six women who did not become pregnant) were excluded from analysis the pregnancy rate (ongoing) was 24 (19%). These results indicate that exogenous oestradiol can safely be used for the synchronization of endogenous and exogenous FSH stimuli in COH. This approach provides the practical advantage of permitting an advanced timing of the onset of COH treatments when gonadotrophin-releasing hormone (GnRH) agonists are not used, which improves treatment convenience for patients and team members alike. Further development of this model may enable control of the onset of natural cycles which may find practical applications for timing assisted reproductive techniques (intrauterine insemination or in-vitro fertilization) in the natural cycle.

Gonadotropin secretion in infantile rats exposed to ethanol in utero

Previous studies have shown that fetal alcohol exposure (FAE) alters reproductive function in both male and female rats. In females, FAE delays the onset of puberty, reduces a preovulatory-like LH surge, and results in an early onset of acyclicity. In males exposed to ethanol in utero, the perinatal surge of testosterone is reduced. During the infantile period of the female rat, there is a dramatic increase in plasma follicle-stimulating hormone (FSH), which is thought to play a role in initiating ovarian activity and perhaps the onset of puberty. In this study, we determined the effects of FAE on the patterns of gonadotropin secretion during the infantile period [postnatal days (PND) 8–21] in both male and female rats. Timed pregnant dams were fed a liquid diet containing 35% ethanol-derived calories during the final week of gestation. Control dams were fed either an isocaloric diet with sucrose substituted for ethanol (pair fed, PF) or laboratory chow (chow fed, CF). Male and female pups were sacrified on PND 8, 10, 12, 15, 18, and 21, and trunk blood was collected. In males, LH levels decreased to a nadir on PND 18, and this decrease was blunted by FAE ( p < 0.05). In contrast, FSH secretion was not altered by FAE. In females, plasma FSH levels were greater than males, and increased to peak on PND 12. This FSH peak was significantly delayed in FAE females ( p < 0.02). There was no age-related change in LH levels in FAE females, and LH levels were not altered by FAE. The delayed peak of FSH secretion by FAE correlates with the delay in puberty previously seen in females. To investigate this further, we examined the possibility that the delay in the peak of serum FSH in FAE females is due to a reduced number of FSH-producing gonadotrophs. FSH-containing gonadotrophs were identified by immunocytochemistry. Cell counts of FSH-immunoreactive cells in pituitaries from PND 8, 15, and 21 control-fed and FAE female rats showed developmental increases in the number of FSH gonadotrophs per unit area ( p < 0.001), but no treatment differences were observed. Overall, these data show that fetal alcohol exposure can alter gonadotropin secretion in infantile life in male and female rats. Importantly, the delay in FSH secretion in females may ultimately play a role in the delay in puberty observed in the FAE female rat.

Effects of passive immunization against oestradiol-17beta and inhibin on the secretion of gonadotrophin in the cyclic golden hamster (Mesocricetus auratus).

To investigate the physiological importance of oestradiol-17beta and inhibin in the regulation of gonadotrophin secretion in the cyclic golden hamster, females were passively immunized against two hormones. When 200 microL antiserum against oestradiol-17beta (oestradiol-AS) was given on Day 3 (Day 1 = day of ovulation), the preovulatory gonadotrophin surge was completely blocked for 24 h and the length of the oestrous cycle was also prolonged for one day. In the group given 200 microL oestradiol-AS on Day 3, basal levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increased slightly and superovulation (19.6+/-0.8, mean+/-s.e.m.) occurred. When 200 microL antiserum against inhibin (inhibin-AS) was given at 1100 hours on Day 3, a dramatic increase in plasma FSH and a slight increase in LH were noted, resulting in superovulation (38.2+/-2.6) on the expected Day 1. The present study indicates clearly that inhibin plays a major role in regulating the specific ovulation rate in the hamster through the control of FSH secretion. Present results also indicate that oestradiol-17beta suppresses basal LH secretion. Oestradiol-17beta may act as an indicator of the follicular maturation, and the high plasma concentration of oestradiol-17beta noted from Day 3 to Day 4 may play an important role in determining the timing of initiation of the preovulatory gonadotrophin surge.

Dibromochloropropane (DBCP): A 17-year Reassessment of Testicular Function and Reproductive Performance

The current study summarizes a 17-year reevaluation of testicular function and reproductive performance of 15 production workers with dibromochloropropane (DBCP)-induced testicular dysfunction. Sperm count recovery was evident within 36 to 45 months in three of the nine azoospermic and in three of the six oligozoospermic men with no improvement thereafter. A significant increase in plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a nonsignificant decrease in testosterone level were detected in the severely affected individuals. There was no increase in the rate of spontaneous abortions and congenital malformations among pregnancies conceived during or after exposure. A low prevalence of male infants conceived during paternal exposure was found as compared with the preexposure period (16.6% versus 52.9%; P<.025). Restoration of fertility was followed by a gradual increase of this value to 41.4%.

Intratesticular Control Of Steroidogenesis

Men are men because of testosterone, and the effects of this hormone are evident in virtually every organ or tissue in a normal adult man. Because testosterone is a classical endocrine hormone with effects throughout the body, many endocrinologists will have failed to realize that, in terms of its effects on fertility, the primary role of testosterone is not endocrine but paracrine, as it is the local action of testosterone on spermatogenesis which determines fertility. When looked at from this perspective it is logical to question the traditional endocrine teaching which states that testosterone secretion is controlled solely by pituitary luteinizing hormone (LH). Certainly, the levels of testosterone and LH in peripheral blood show a close relationship, but it is not the level of testosterone in peripheral blood which determines fertility. If the primary role of testosterone is within the testis, then it is not unreasonable to expect that local mechanisms may exist to regulate the intratesticular levels of this steroid. The object of this review is to examinecritically the evidence for such mechanisms, their possible nature and their physiological and clinical significance (if any). Before reviewing the data on intratesticular control of steroidogenesis it is essential to place it in perspective. To do this, three principal questions need to be answered: (I) Why might intratesticular mechanisms for local control of testosterone production be required? (2) What is the role (or roles) of testosterone within the testis? A proper understanding of how testosterone controls spermatogenesis is essential if the local regulation of testosterone production is to be evaluated from a physiological perspective. (3) What are the constraints or problems relating to studies on the intratesticular control of steroidogenesis? It is essential to understand the potential limitations of studies on this subject so that a reasoned interpretation of the results can be made. Most relevant data is derived from studies in uitro, and the relationship of such data to the situation in uivo is often difficult to establish.

Effects of a major androgen-dependent urinary protein, α 2u-globulin on the pituitary-gonadal axis and hypothalamic monoamines in adult male mice

The purpose of the present study was to evaluate the effects of alpha-2u-globulin, a sex-dependent male rat urinary protein on pituitary-gonadal functions and hypothalamic monoamine contents in male mice. Adult male mice, maintained under standardized laboratory conditions (L:D, 14:10)were injected subcutaneously with alpha-2u-globulin at a dose of 1 mg/animal/day or with vehicle daily for 14 days and killed 16 h after the last injection. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and testicular levels of T were measured by radioimmunoassays. The concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in medial basal hypothalamus (MBH) and anterior hypothalamus (AH) were measured by high performance liquid chromatography. Administration of alpha-2u-globulin led to a significant increase in plasma FSH and LH levels (P<0.05) as well as in plasma and testicular T levels (P<0.025). In the MBH of alpha-2u-globulin treated mice, there were significant elevations of NE (P<0.025), DA (P<0.01) and 5-HT (P<0.025) contents. In the AH, both DA (P<0.025) and (P<0.01) contents were decreased while NE content remained unaltered. These results indicate that administration of alpha-2u-globulin can lead to a significant stimulation of pituitary-testicular axis and that this effect may be mediated through alteration of hypothalamic monoamines.

Passive immunoneutralization of endogenous inhibin: sex-related differences in the role of inhibin during development

The purpose of these studies was to ascertain the extent to which endogenous inhibin regulates follicle-stimulating hormone (FSH) secretion at different intervals during development in the male and female rat. This was determined by examining the changes in plasma FSH that resulted from immunoneutralizing endogenous inhibin in male and female rats at different ages during development and into adulthood. Passive immunoneutralization of endogenous inhibin was achieved using specific, high titer ovine antiserum, generated against the α-subunit of the recently described inhibin molecule. Optimal antiserum volumes and time after injection required to observe maximal changes in FSH secretion were determined in initial experiments. No clear effect of immunoneutralizing endogenous inhibin could be demonstrated on FSH secretion in female rats until 20 days of age, after the completion of the endogenous rise in FSH which occurs between days 5 and 20. Thereafter, injection of the anti-α-inhibin serum (anti-αIN) produced a progressively marked increase in plasma FSH as the age of the females increased. In male rats, injection of the anti-αIN serum caused an increase in FSH secretion as early as 5 days of age, although the response was more delayed at this age than at later times. The ability of the anti-αIN serum to increase plasma FSH was observed through 20 days of age. At 30 days of age, during the peak of the endogenous rise in plasma FSH, injection of the anti-αIN serum failed to further increase the already elevated levels of plasma FSH. As the endogenously high levels of FSH gradually decreased, the ability of anti-aIN serum to increase FSH secretion returned (40 days of age) but was diminished by 50 days of age and was completely lost by 60 days of age. The results of the present study indicate that inhibin plays an increasingly important role as a regulator of FSH secretion in the female from at least 20 days of age into adulthood. In the male, however, the role of inhibin in regulating FSH secretion, which is clearly present during early postnatal development, is apparently lost at the time of puberty.

Tamoxifen Citrate Therapy in Male Infertility

A prospective, randomized, double-blind study with crossover, using tamoxifen (TAM) (Nolvadex, ici Pharma, Missisauga, Canada) 20 mg/day and placebo (p) for 6 months each, was conducted in 16 infertile men with idiopathic oligozoospermia. Baseline sperm count was 17.092 +/- 3.09 (10(6)/ml). Hormonal profile was performed and included follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), thyroid-stimulating hormone (TSH), and luteinizing hormone-releasing hormone (LH-RH) stimulation tests. The sperm analysis and hormonal profile were repeated at 6 and 12 months of the study. A sperm penetration assay (SPA) was performed on zona-free hamster egg. Compared with the placebo group, the TAM group showed a significant increase in plasma FSH, LH, E2, and T levels (P less than 0.001), but not in PRL and TSH levels. However, LH-RH stimulation tests and SPA were found to be comparable in the two treatment groups, and there was no significant effect on sperm analysis. Tamoxifen appeared to be no more effective than the placebo in the treatment of idiopathic oligozoospermia.

Tamoxifen citrate therapy in male infertility

A prospective, randomized, double-blind study with crossover, using tamoxifen (TAM) (Nolvadex, ici Pharma, Missisauga, Canada) 20 mg/day and placebo (p) for 6 months each, was conducted in 16 infertile men with idiopathic oligozoospermia. Baseline sperm count was 17.092 +/- 3.09 (10(6)/ml). Hormonal profile was performed and included follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), thyroid-stimulating hormone (TSH), and luteinizing hormone-releasing hormone (LH-RH) stimulation tests. The sperm analysis and hormonal profile were repeated at 6 and 12 months of the study. A sperm penetration assay (SPA) was performed on zona-free hamster egg. Compared with the placebo group, the TAM group showed a significant increase in plasma FSH, LH, E2, and T levels (P less than 0.001), but not in PRL and TSH levels. However, LH-RH stimulation tests and SPA were found to be comparable in the two treatment groups, and there was no significant effect on sperm analysis. Tamoxifen appeared to be no more effective than the placebo in the treatment of idiopathic oligozoospermia.

Endocrine responses in relation to compensatory testicular growth after neonatal hemicastration in boars.

Mass (TM) and relative mass (organ mass/body mass; RTM) of the right testis and epididymis (EM and REM, respectively) were determined every 14 days from 10 to 122 days of age for intact boars (I) and boars hemicastrated on Day 10 (HC) in two crossbred herds (Trial 1 and Trial 2). Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, growth hormone (GH), and testosterone were determined in four blood samples from each pig, three collected 24 h prior to castration and one immediately prior to castration. Values for TM and RTM of HC boars were approximately double (p less than 0.0001) those of I boars by 38 days of age, and these differences were maintained through Day 122. Both EM and REM were greater (p less than 0.05) in HC than in I boars from Day 52 to Day 122. The TM, RTM, EM and REM were greater (p less than 0.05) in Trial 1 than in Trial 2 for both I and HC boars from Day 80 to Day 122, indicating an earlier onset of pubertal testicular growth in the Trial-1 boars. Plasma GH concentration was greater (p less than 0.05) in HC than in I boars from Day 16 to Day 38. A transient increase in plasma FSH (p less than 0.05) was observed from Day 24 to Day 38. After Day 38, there was no difference (p greater than 0.05) in FSH or GH between HC and I boars, or between trials. Plasma LH, prolactin, and testosterone concentrations were also similar in HC and I boars.(ABSTRACT TRUNCATED AT 250 WORDS)