Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males

Two half-brothers with short stature secondary to growth hormone deficiency and a family history implicating X-linked transmission were studied extensively for other endocrine abnormalities. The proband had a normal physical examination, except for small stature and small external genitalia. ACTH and TSH release were normal. LH and FSH responses during an i.v. GnRH test were severely blunted. His half-brother also had a normal physical examination, except for severe short stature and very small external genitalia. Deficiencies of ACTH, and TSH as well as GH were documented. An i.v. GnRH test showed no LH or FSH response. These studies support the existence of an X-linked recessive form of hypopituitarism and portend the clinical usefulness of the i.v. GnRH test in evaluating gonadotropin reserve.     

Endocrine abnormalities in mitochondrial myopathy with external ophthalmoplegia

Summary Endocrine functions were examined in 21 patients with mitochondrial myopathies presenting with chronic progressive external ophthalmoplegia and other additional neurological and multisystemic symptoms. Ten patients had the features of the Kearns-Sayre syndrome. Deletions of the mitochondrial DNA were found in 4 out of 5 patients examined. Fourteen patients, including 3 with deletions of the mitochondrial DNA, had various and often multiple endocrine abnormalities: 6 patients were of short stature, 3 had irregular menstrual cycles, 3 had undersized testicles, 5 showed an insufficient rise of growth hormone following the administration of growth-hormone-releasing hormone, 4 showed an insufficient rise in FSH after administration of gonadotropin-releasing hormone, 5 had manifest diabetes mellitus, 3 showed an impaired glucose tolerance, and 2 patients had subnormal serum levels of parathormone in combination with hypocalcaemia. One patient additionally had Klinefelter's syndrome with a kariotype 47, XXY and increased levels of FSH and LH, subnormal levels of testosterone and subnormal testicular volume. The occurrence of endocrine defects correlated with the duration of disease. The data demonstrate that endocrine abnormalities are frequently associated with mitochondrial myopathy, indicating that this multisystemic disease also involves various endocrine tissues.Abbreviations ACTH adrenocorticotropic hormone - CoQ coenzyme Q₁₀ - CRH corticotropin-releasing hormone - FSH follicle-stimulating hormone - GH growth hormone - GHRH growth-hormone-releasing hormone - GnRH gonadotropin-releasing hormone - LH luteinizing hormone - mtDNA mitochondrial DNA - PTH parathormone - TRH thyrotropin-releasing hormone - TSH thyroid-stimulating hormone - T₃ triiodothyronine - T₄ thyroxine     

Detection of gonadotropin-releasing hormone receptor in normal human pituitary cells and pituitary adenomas using immunohistochemistry

Gonadotropin-releasing hormone (GnRH), which is a well-known regulator of gonadotroph function, has recently been considered to be a paracrine factor involved in the control of somatotroph, lactotroph, and corticotroph cells. GnRH action is initiated by binding to a specific cell surface receptor, the gonadotropin-releasing hormone receptor (GnRHR), which is expressed by follicle-stimulating hormone/luteinizing hormone (FSH/LH) cells. Using in situ hybridization techniques, GnRHR messenger ribonucleic acid (mRNA) has recently been detected in normal human anterior pituitary gland and in various pituitary adenomas, including FSH/LH-cell, growth hormone (GH)-cell, adrenocorticotropic hormone (ACTH)-cell, and null-cell adenomas. However, immunohistochemical studies indicating the specific cell distribution of GnRHR in normal pituitary cells have never been reported. The aim of the present investigation was to evaluate the immunohistochemical expression of GnRHR in different types of normal pituitary cells and related tumors. Using double-label immunohistochemical techniques on formalin-fixed and paraffin-embedded tissues and specific antibodies directed against pituitary hormones and GnRHR, we found GnRHR immunoreactivity not only in FSH/LH cells, but also in GH- and thyroid-stimulating hormone (TSH) cells. GnRHR was detected in FSH/LH-cell, GH-cell, mixed GH- and prolactin (PRL)-cell, and α-subunit (α-SU)/null-cell adenomas. The findings of this study suggest that the interaction between GnRH and GnRHR may play a role in paracrine/autocrine regulation of different types of normal pituitary cells and pituitary adenomas. Received: 24 January 2000 / Accepted: 12 April 2000     

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure.

A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.     

三叶因子3在大鼠腺垂体嗜色细胞中的定位

目的探讨三叶因子3(TFF3)在腺垂体远侧部嗜酸性细胞和嗜碱性细胞中的表达,明确TFF3在远侧部的分布。方法采用相邻切片的免疫组织化学染色,在相邻切片上分别显示TFF3/生长激素(GH)、TFF3/催乳素(PRL)、TFF3/促甲状腺激素(TSH)、TFF3/促肾上腺皮质激素(ACTH)、TFF3/卵泡刺激素(FSH)、TFF3/黄体生成素(LH)的表达。结果 TFF3和各嗜色细胞的免疫反应产物为棕黄色,主要位于细胞质,ACTH免疫阳性信号在胞膜也有表达,主要分布在腺垂体的远侧部。邻片显示TFF3存在于部分GH、PRL、TSH、ACTH、FSH、LH细胞,分别占19.4%、22.4%、9.2%、6.5%、35.7%、8.3%,以FSH最多,PRL、GH次之。结论垂体远侧部TFF3可分别表达于GH、PRL、TSH、ACTH、FSH、LH细胞。     

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure

A 35-month-old black boy with Hallermann–Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T₄ and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be some what altered due to his racial background. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.     

Expression of vascular endothelial growth factor in normal pituitary cells and pituitary adenomas producing adrenocorticotropic hormone

Vascular endothelial growth factor (VEGF) induces endothelial cell proliferation and an increase in capillary permeability. Because the anterior pituitary gland and pituitary adenomas are highly vascular, expression of VEGF was examined immunohistochemically. Some normal pituitary cells stained positively for VEGF, and restaining for ACTH, prolactin, TSH, LH, FSH, and S-100 protein after VEGF staining revealed that almost all cells staining positively for ACTH also stained for VEGF. Only adenomas staining positively for ACTH stained for VEGF. These results suggest that VEGF is produced by normal pituitary cells and adenomas producing ACTH.     

Secretion of anterior pituitary hormones in man: effects of ethyl alcohol.

The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5 g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radioimmunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113-270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 p.m., p less than 0.01). This increase was not seen after alcohol ingestion (p less than 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 vs. 106 ng/ml, p less than 0.01 and 74 vs. 121 ng/ml, p less than 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, WE SUggest that ethanol exerts these effects on a suprapituitary site.     

Secretion of Anterior Pituitary Hormones in Man: Effects of Ethyl Alcohol

The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radio-immunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113–270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 pm., p < 0.01). This increase was not seen after alcohol ingestion (p < 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 us, 106 ng/5ml, p < 0.01 and 74 us, 121 ng/ml, p < 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, we suggest that ethanol exerts these effects on a suprapituitary site.     

Effect of antagonists of dopamine and opiates on the basal and GnRH-induced secretion of luteinizing hormone, follicle stimulating hormone and prolactin during lactational amenorrhoea in breastfeeding women

The role of dopamine and opiates in the suckling-induced suppressionof gonadotrophin secretion and prolactin release was investigatedduring lactational amenorrhoea in fully breastfeeding womenat 12 weeks post-partum. A total of 26 women, 20 using non-steroidalmethods of contraception and six using the progestogen-onlypill, Noriday (POP), breastfed their babies on demand at a frequencyof 3.6 ± 0.2 suckling episodes during the 8 h study periodwhile blood samples were collected at 10-min intervals. Fivehours after the start of sampling six women were given the dopamineantagonist metoclopramide (10 mg, i.m.) while four women receivedsaline. In a second experiment, six women using nonsteroidalcontraception and three women on the POP received an i.v. infusionof the opiate antagonist naloxone (1.6 mg/h) for 2 h, whilefour women using non-steroidal contraception and three womenon the POP were infused with saline. Two hours after the i.m.injection or start of infusion all women were given an i.v.injection of 10 µg gonadotrophin releasing hormone (GnRH)and samples were collected for a further 1 h. All samples wereassayed for luteinizing hormone (LH), follicle stimulating hormone(FSH) and prolactin. Plasma concentrations of oestradiol were<60 pmol/l in all women and they remained amenorrhoeic forat least 10 weeks after the study. Pulsatile release of LH wasonly observed over the 5 h pre-treatment period in 10 of the20 non-steroid taking women (1–3 pulses/5 h), and in oneof the six women (1 pulse/5 h) on POP. Treatment with metoclopramidecaused a substantial (29-fold) increase in prolactin over baseline,7.4 times the maximum released in response to suckling. Therewas no effect of metoclopramide on the pattern of release ofLH or FSH or the response to GnRH. Infusion of naloxone in womenusing either non-steroidal contraceptives or progestogen-onlypill did not affect prolactin release. Naloxone infusion didnot affect LH or FSH in women using nonsteroidal contraceptives,but caused a small but significant (P < 0.05) increase inboth LH and FSH in women taking the progestogen-only pill. Therewas a significantly greater release of LH and FSH after GnRHin all women after naloxone infusion. These results in breastfeedingwomen during lactational amenorrhoea confirmed that sucklingsuppresses the pulsatile release of LH but not through a dopaminergicpathway, showed that prolactin remains under dopaminergic controlduring human lactation, but suckling does not appear to affectprolactin secretion via an opiate pathway and indicated onlya minor, if any, role for opiates in the sucklinginduced suppressionof GnRH/gonadotrophin secretion but a potential, previouslyunreported, effect of opiates in reducing pituitary responsivenessto GnRH.     

中老年男性胰岛素抵抗和相关激素水平变化规律及临床意义的研究

对中老年男性胰岛素抵抗及相关激素水平随年龄增长的变化特点及规律进行了分析, 并对其临床意义进行探讨.用放射免疫法测定血清LH、FSH、T、SHBG、TSH、INS,用葡萄糖氧化酶法测定FBG, 采用内环境稳定模式(HOMA)估测胰岛素抵抗(IR)水平.结果显示: IR、LH、FSH、SHBG随年龄增大逐渐增高, T、TSH随年龄增长逐渐降低, 与对照组比较除TSH变化不明显外, 其他指标变化均具有一定规律, 对中老年男性机体基础状况具有临床评价意义.     

Martsolf syndrome in Japanese siblings

We describe a Japanese brother and sister with Martsolf syndrome. They had short stature, severe mental retardation, cataract, hypogonadism, craniofacial dysmorphism, and bone and joint symptoms including scoliosis, lax finger joints, and talipes valgus. Previously undescribed findings included proximal femoral epiphyseal dysplasia reminiscent of Legg-Calve-Perthes disease in both patients, and Klippel-Feil malformation and osteopathia striata in one patient. Brain MRI showed mild frontal and temporal lobe atrophy, and mild ventricular enlargement. Severe GH deficiency was demonstrated after insulin tolerance and glucagon/propranolol tolerance tests. No responses to serum LH and FSH after a gonadotropin-releasing hormone (GnRH) test suggested secondary hypogonadism, that is, hypogonadotropic hypogonadism, due to hypothalamus-pituitary axis insufficiency in both patients.     

A new X-linked mental retardation (XLMR) syndrome with late-onset primary testicular failure, short stature and microcephaly maps to Xq25-q26

X-linked mental retardation (XLMR) is a heterogeneous disorder with both syndromic and non-syndromic forms. Here we describe the clinical and molecular characterisation of a family with a syndromic form of XLMR with hypogonadism and short stature. We investigated a family in which four male members in two generations presented with hypergonadotrophic hypogonadism associated with development of small and abnormal testes. In two of the males, late-onset testicular ascent was noted. In addition, all affected males had short stature (<0.4th centile) and mild learning difficulties and three out of the four had microcephaly. Karyotypes were normal and endocrine investigations confirmed primary testicular failure. The phenotype segregated as an X-linked trait. Haplotype and genetic two-point linkage analysis with 22 microsatellites excluded the whole X chromosome except for a region on Xq25-Xq27 encompassing 13.7Mb with a maximum LOD score of 1.1 for marker DXS8038 at theta=0.05. One family previously described as having XLMR with hypogonadism and short stature maps to the same X chromosome region implicated in our family. However, the more severe mental retardation, muscle wasting and tremor described in this other family would suggest that our family is affected by a novel XLMR syndrome.     

Modulation of the action of gonadotrophin surge-attenuating factor by gonadotrophin-releasing hormone

Gonadotrophin surge-attenuating factor (GnSAF) is a putativenon-steroidal ovarian factor which attenuates the luteinizinghormone (LH) surge in superovulated women through the reductionof the pituitary response to gonado-trophin-releasing hormone(GnRH). The mechanism of action of GnSAF on gonadotrophin secretionwas further studied by investigating six normally ovulatingwomen in two cycles a spontaneous and a follicle-stimulatinghormone (FSH)-treated cycle. The response of the pituitary tofive consecutive pulses of GnRH was investigated in late follicularphase (follicle size 15 mm) of both cycles. GnRH pulses, 10µg each, were injected i.v. every 2 h and LH was measuredin blood samples taken before and 30, 60 and 120 min after eachpulse. FSH was injected daily at the fixed dose of 225 IU startingon cycle day 2. Peak values of LH increment occurred 30 minafter each pulse. However, maximal LH increment occurred inboth cycles after the second GnRH dose. In the FSH cycles theresponse of LH to the first three pulses was significantly attenuatedcompared with the spontaneous cycles, while the response tothe fourth and fifth pulses was similar in the two cycles. Inboth cycles, LH increment 30 min post GnRH (net increase abovethe previous value) was similar after the fourth and fifth pulses.Serum concentrations of oestradiol and immunoreactive inhibin,although higher in the FSH cycles, remained stable throughoutthe GnRH experimental period in both cycles. These results demonstratethat multiple submaximal doses of GnRH can override the attenuatingeffect of GnSAF on LH secretion. From a physiological pointof view, this is possibly part of the mechanism which controlsthe action of GnSAF at mid-cycle.     

Role of gonadotrophin releasing hormone baseline concentrations in the control of pituitary gonadotrophin and ovarian steroid secretion in the pseudopregnant rat

To study the effect of moderately elevated gonadotrophin releasinghormone (GnRH) baseline concentrations during the luteal andthe follicular phase, pseudopregnant rats were infused s.c withGnRH at several doses for 5 days. These rats were also treatedwith oestradiol or sham-treated during the last 3 days of GnRHtreatment GnRH infusions started on day 7 or day 3 of the lutealphase of the ovulatory cycle; in the rat, the luteal phase orpseudopregnancy lasts about 10 days. Luteinizing hormone (LH)and follicle stimulating hormone (FSH) responses were inducedby i.v. injection of GnRH on day 12 (after expected luteolysis)or on day 8 (before expected luteolysis). In normal rats theLH and FSH responses induced by GnRH on day 12 were higher thanon day 8 (160 and 50% respectively). In GnRH-infused rats theLH and FSH responses were not increased. In these rats the lutealphase was extended (the plasma progesterone concentrations remainedhigh) and the onset of the follicular phase was postponed (plasmaoestrogen concentrations did not increase). Oestradiol increasedthe day 12 LH and FSH responses; this effect of oestradiol wassuppressed by GnRH infusion. On day 8, exogenous oestradiolalso increased the LH and FSH responses, but again the effectof oestradiol was suppressed when the animals were concomitantlyinfused with GnRH. These data may suggest that in the rat, GnRHbaseline concentrations participate in the neuroendocrine systemcontrolling gonadotrophin secretion and hence the ovulatorycycle.     

Short stature, brachydactyly, small ears, and a pattern of minor anomalies in brother and sister born to consanguineous parents: a hitherto unreported syndrome?

A 13-year-old boy and his 28-year-old sister had short stature, obesity, and a pattern of minor anomalies including a sloping, narrow forehead; small ears; a narrow nose with prominent bridge and long septum; short upper lip; receding mandible; and short limbs with brachydactyly and clinodactyly of little fingers. The boy also had hypoplastic external genitalia and elevated FSH. Both are of normal intelligence. There is remote consanguinity of the (normal) parents. The 2 sibs probably represent a hitherto un-recognized syndrome of possibly autosomal recessive inheritance.     

Combined pituitary function-test with four hypothalamic releasing hormones

Summary Anterior pituitary function was investigated in ten healthy subjects by administering a combination of 200 µg thyrotropin releasing hormone (TRH), 100 µg gonadotropin releasing hormone (GnRH), 100 µg growth hormone releasing factor (GRF^1–44), and 100 µg human corticotropin releasing factor (CRF). The same test protocol was performed in all subjects after pretreatment with 0.25 mg terguride. Five subjects were tested only with TRH and GnRH, five only with CRF, and six only with GRF. There was a prompt increase in all hormones after the administration of the four releasing hormones (RH). Pretreatment with terguride lowered the prolactin (PRL) increase (p<0.01) as well as the thyrotropin (TSH) peak (p<0.05) compared with the test without dopamine agonist pretreatment. The PRL levels after combined RH administration were significantly higher than after TRH and GnRH alone. Although four of the five subjects had higher TSH levels after combined RH administration than after TRH and GnRH alone, the difference was not significant. Other hormones were not significantly influenced by the combined RH administration or dopamine agonist pretreatment. Despite the fact that the interaction of the different releasing hormones and dopamine agonists influences the pituitary hormone response, combined RH administration seems to be a useful test for evaluating pituitary function also in patients receiving dopamine agonist therapy.Abbreviations ACTH Adrenocorticotropic hormone - CRF Human corticotropin releasing factor - DA Dopamine - FSH Follicle-stimulating hormone - GH Human growth hormone - GnRH Gonadotropin releasing hormone - GRF; GRF^1–44 Growth hormone releasing factor - LH Luteinizing hormone - PRL Prolactin - RH Releasing hormone (s) - RIA Radioimmunoassay - SE Standard error - TRH Thyrotropin releasing hormone - TSH Thyrotropin Supported by Deutsche Forschungsgemeinschaft (We 439/5-1 and Mu 585/2-2).     

180例垂体腺瘤的临床病理观察

目的：研究垂体腺瘤的临床激素过多症状与腺瘤组织激素检测之间的关系以及该病的发生、生物学行为分类。方法：对180例垂体腺瘤进行了临床病理分析。并对其中110例应用免疫组化ABC法检测了肿瘤的GH、PRL、ACTH、TSH、FSH、LH。结果：临床激素过多症状与激素检测相一致者占40%,且女性较男性相致者多,差异有显著性。免疫组化分型以PRL和GH腺瘤多见,多激素腺瘤以GH PRL腺瘤多见。结论：垂体腺瘤的免疫组化检测与形态功能相结合的分类方法简便易行较为实用。     

XY/XYY mosaicism associated with major genital defects

A 9-year-old boy with short stature and abnormal genitalia was found to have an XY/XYY chromosomal constitution. On physical examination, in addition to his short stature he had a shield chest and external genitalia showing a hypospadias with cryptorchidism on the left side. The right testicle was present in the scrotum. His intellectual performance was normal and there wax no history of abnormal behavior. Surgical exploration revealed in the left side a streak gonad with a vas deferens and a fallopian tube. Fluorescencc studies of interphasic nuclei and chromosomes confirmed the XY/XYY karyotype. Two hypotheses are advanced to account for this mosaicism.     

Luteinizing hormone response to gonadotrophin-releasing hormone in normal women undergoing ovulation induction with urinary or recombinant follicle stimulating hormone

Oestradiol enhances pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) in normal women, while in women undergoing ovulation induction the putative factor gonadotrophin surge attenuating factor (GnSAF) attenuates the response of luteinizing hormone (LH) to GnRH. To study the relationships between oestradiol and GnSAF during ovulation induction, 15 normally ovulating women were investigated in an untreated spontaneous cycle (control, first cycle), in a cycle treated with daily i.m. injections of 225 IU urinary follicle-stimulating hormone (FSH) (Metrodin HP, uFSH cycle) and in a cycle treated with daily s.c. injections of 225 IU recombinant FSH (Gonal-F, rFSH cycle). Treatment with FSH started on cycle day 2. The women during the second and third cycle were allocated to the two treatments in an alternate way. One woman who became pregnant during the first treatment cycle (rFSH) was excluded from the study. In all cycles, an i.v. injection of 10 microg GnRH was given to the women (n = 14) daily from days 2-7 as well as from the day on which the leading follicle was 14 mm in diameter (day V) until mid-cycle (n = 7). The response of LH to GnRH at 30 min (deltaLH), representing pituitary sensitivity, was calculated. In the spontaneous (control) cycles, deltaLH values increased significantly only during the late follicular phase, i.e. from day V to mid-cycle, at which time they were correlated significantly with serum oestradiol values (r = 0.554, P < 0.01). Initially during the early follicular phase in the uFSH and the rFSH cycles, deltaLH values showed a significant decline which was not related to oestradiol (increased GnSAF bioactivity). Then, deltaLH values increased significantly on cycle day 7 and further on day v with no change thereafter up to mid- cycle. On these two days, deltaLH values were correlated significantly with serum oestradiol values (r = 0.587 and r = 0.652 respectively, P < 0.05). During the pre-ovulatory period, deltaLH values in the FSH cycles were significantly lower than in the spontaneous cycles. Significantly higher serum FSH values were achieved during treatment with uFSH than rFSH. However, serum values of oestradiol, immunoreactive inhibin, and deltaLH as well as the number of follicles > or = 12 mm in diameter did not differ significantly between the two FSH preparations. These results suggest that in women undergoing ovulation induction with FSH, oestradiol enhances pituitary sensitivity to GnRH, while GnSAF exerts antagonistic effects. The rFSH used in this study (Gonal-F) was at least as effective as the uFSH preparation (Metrodin-HP) in inducing multiple follicular maturation in normally cycling women.