Thyrotropin-releasing Hormones Research Articles

HBM4EU Chromates Study: Urinary Metabolomics Study of Workers Exposed to Hexavalent Chromium.

Exposure to hexavalent chromium Cr(VI) may occur in several occupational activities, placing workers in many industries at risk for potential related health outcomes. Untargeted metabolomics was applied to investigate changes in metabolic pathways in response to Cr(VI) exposure. We obtained our data from a study population of 220 male workers with exposure to Cr(VI) and 102 male controls from Belgium, Finland, Poland, Portugal and the Netherlands within the HBM4EU Chromates Study. Urinary metabolite profiles were determined using liquid chromatography mass spectrometry, and differences between post-shift exposed workers and controls were analyzed using principal component analysis. Based on the first two principal components, we observed clustering by industrial chromate application, such as welding, chrome plating, and surface treatment, distinct from controls and not explained by smoking status or alcohol use. The changes in the abundancy of excreted metabolites observed in workers reflect fatty acid and monoamine neurotransmitter metabolism, oxidative modifications of amino acid residues, the excessive formation of abnormal amino acid metabolites and changes in steroid and thyrotropin-releasing hormones. The observed responses could also have resulted from work-related factors other than Cr(VI). Further targeted metabolomics studies are needed to better understand the observed modifications and further explore the suitability of urinary metabolites as early indicators of adverse effects associated with exposure to Cr(VI).

Correlation of Expression Changes between Genes Controlling 5-HT Synthesis and Genes Crh and Trh in the Midbrain Raphe Nuclei of Chronically Aggressive and Defeated Male Mice.

Midbrain raphe nuclei (MRNs) contain a large number of serotonergic neurons associated with the regulation of numerous types of psychoemotional states and physiological processes. The aim of this work was to study alterations of the MRN transcriptome in mice with prolonged positive or negative fighting experience and to identify key gene networks associated with the regulation of serotonergic system functioning. Numerous genes underwent alterations of transcription in the MRNs of male mice that either manifested aggression or experienced social defeat in daily agonistic interactions. The expression of the Tph2 gene encoding the rate-limiting enzyme of the serotonin synthesis pathway correlated with the expression of many genes, 31 of which were common between aggressive and defeated mice and were downregulated in the MRNs of mice of both experimental groups. Among these common differentially expressed genes (DEGs), there were genes associated with behavior, learning, memory, and synaptic signaling. These results suggested that, in the MRNs of the mice, the transcriptome changes associated with serotonergic regulation of various processes are similar between the two groups (aggressive and defeated). In the MRNs, more DEGs correlating with Tph2 expression were found in defeated mice than in the winners, which is probably a consequence of deeper Tph2 downregulation in the losers. It was shown for the first time that, in both groups of experimental mice, the changes in the transcription of genes controlling the synthesis and transport of serotonin directly correlate with the expression of genes Crh and Trh, which control the synthesis of corticotrophin- and thyrotropin-releasing hormones. Our findings indicate that CRH and TRH locally produced in MRNs are related to serotonergic regulation of brain processes during a chronic social conflict.

Changes in thyroid axis responses in two ring-billed gull sub-populations differentially exposed to halogenated flame retardants

Developing bird embryos may be affected by a number of thyroid disrupting chemicals through maternal transfer. However, thyroid disruption in developing embryos of wild birds remains largely unstudied, especially with respect to exposure to ubiquitous environmental contaminant classes including halogenated flame retardants (HFRs). The objective of the present study was to investigate responses of the hypothalamic-pituitary-thyroid (HPT) axis of developing birds that are exposed to elevated concentrations of HFRs in their environment. Ring-billed gulls (Larus delawarensis) were collected at the external pipping stage (i.e., just prior to hatching) from two sub-populations that are differentially exposed to HFRs in the St. Lawrence River (QC, Canada). Plasma levels of thyroid hormones (THs) and transcription levels of thyroid-related genes in three tissues (i.e., liver, thyroid gland and brain) were related to liver concentrations of HFRs in pipping gulls from these two colonies. Liver polybrominated diphenyl ether (PBDE) concentrations were negatively correlated with plasma total T4 and total T4/T3 in pipping ring-billed gulls. Moreover, plasma TH levels and hepatic PBDE concentrations were correlated with the transcription of genes involved in metabolism (deiodinases type 1, 2 and 3) and synthesis (sodium iodide symporter and thyroglobulin) in the thyroid gland, negative feedback loop (thyrotropin and corticotropin releasing hormones) in the brain and the pituitary and targeted action (TH receptors) in the three tissues of gulls. The present study suggested that the alteration of TH homeostasis in developing wild birds through changes in the transcription of several thyroid-related genes may be related to potential PBDE-mediated effects.

Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease

Thyrotropin-releasing hormones (TRH) added to prenatal corticosteroids has been suggested as a way to further reduce breathing problems and neonatal lung disease in infants born preterm. To assess the effects of giving prenatal TRH in addition to corticosteroids to women at risk of preterm birth for the prevention of neonatal respiratory disease. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013) and reference lists of retrieved studies. We also contacted trial authors. Randomised controlled trials in women at sufficient risk of preterm birth to warrant the use of prenatal corticosteroids to promote lung maturity. TRH and corticosteroids were compared with corticosteroids, with or without placebo. All assessments of trial eligibility, risk of bias and data extractions were independently carried out by at least two review authors. Over 4600 women were recruited into the 15 trials included in the review, however two trials did not contribute any outcome data to the review. The trials had a moderate risk of bias. Overall, prenatal TRH, in addition to corticosteroids, did not reduce the risk of death prior to hospital discharge (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.86 to 1.27, six trials, 3694 infants), neonatal respiratory distress syndrome (average RR 1.05, 95% CI 0.91 to 1.22, nine trials, 3833 infants), or chronic lung disease (RR 1.01, 95% CI 0.85 to 1.19, five trials, 2511 infants), and did not improve any of the secondary fetal, neonatal or childhood outcomes assessed by intention-to-treat analyses.Indeed, the data showed prenatal TRH to have adverse effects for women and their infants. All side effects reported (nausea, vomiting, light headedness, urgency of micturition, facial flushing) were significantly more likely to occur in women receiving TRH. In the infants, prenatal TRH increased the risk of needing respiratory support (RR 1.16, 95% CI 1.03 to 1.29, three trials, 1969 infants), and of having a low Apgar score at five minutes (RR 1.48, 95% CI 1.14 to 1.92, three trials, 1969 infants). Only three trials provided data on childhood follow-up, and while one trial suggested poorer outcomes for infants who were exposed to prenatal TRH, the other two trials, that assessed infants using an established developmental instrument, showed no clear differences between groups in follow-up outcomes.Sensitivity analyses by trial quality, or subgroups with differing times from entry to birth, or different dose regimens of TRH, did not change these findings. Prenatal TRH in addition to corticosteroids, given to women at risk of preterm birth, does not improve infant outcomes and can cause maternal side effects.

Conversion from Latent to Symptomatic Sheehan's Syndrome by Pegylated Interferon Therapy for Chronic Hepatitis C

A 58-year-old woman with chronic hepatitis C was admitted to our hospital to receive interferon (IFN) therapy. Twenty years earlier she had received blood transfusion because of obstetric hemorrhage. Blood test showed mild hypothyroidism and a relatively elevated eosinophil count. Therapy with pegylated IFNalpha-2a was started, and two days later she complained of nausea and severe malaise. Blood test showed hyponatremia, and plasma prolactin, growth hormone and cortisol levels were all decreased. A simultaneous administration test of lutenizing hormone releasing-, corticotrophin releasing-, growth hormone releasing- and thyrotropin releasing-hormones revealed that only adrenocorticotropic hormone was responsive. Magnetic resonance imaging showed atrophy of anterior lobe of pituitary gland. We diagnosed that IFN therapy disclosed latent Sheehan's syndrome due to previous obstetric hemorrhage. Following supplementation of thyroid and adrenal cortical hormones, we were able to complete IFN therapy. Thus, before IFN therapy for woman patients it is important to suspect latent Sheehan's syndrome when the patient had a history of obstetric hemorrhage.

Pituitary responsiveness to gonadotropin- and thyrotropin-releasing hormones in goats treated with recombinant bovine somatotropin

Non-lactating, crossbred Alpine goats, of similar age and body weight were used to evaluate the effects of bovine somatotropin (bST) administration on pituitary function. Following ovarian synchronization, treated goats ( n=4) received a subcutaneous injection of 160 mg rbST, three times, at 14-day intervals, while control goats ( n=4) remained uninjected. The day after the last rbST injection ovarian synchronization was repeated and the following day all animals were challenged with 50 μg gonadotropin-releasing hormone (GnRH) and 100 μg thyrotropin-releasing hormone (TRH), intravenously. Blood samples were collected at −10, 0, 30, 60, 90, 120, 180, 270 and 360 min after challenge. Additionally, blood sampling was conducted three times per week throughout the experimental period for the detection of peripheral somatotropin, progesterone, T 3 and T 4 concentrations. Treatment with rbST significantly increased somatotropin concentrations in treated animals (21.2±1.3 ng/ml) as compared to controls (5.2±0.4 ng/ml). GnRH and TRH infusions resulted in similar LH, TSH, T 3 and T 4 responses in both groups, in terms of the area under the curve (AUC), the peak value (PV) and the time to peak (PT). Plasma progesterone concentrations during the treatment period did not differ between groups. Treatment with rbST did not affect T 4 levels during the experimental period, but a highly significant effect of treatment was observed for T 3 levels, particularly after the second rbST administration (1.47±0.06 ng/ml versus 2.01±0.1 ng/ml) for the control and treated group. In conclusion, it has been shown that rbST treatment did not affect pituitary responsiveness to GnRH or TRH challenge, demonstrating that the pituitary control of ovarian and thyroid function is not influenced by bST administration.

Dynamic neuroendocrine responses to critical illness

Prolonged critical illness has high morbidity and mortality. The acute neuroendocrine response to critical illness involves an activated anterior pituitary function. In prolonged critical illness, however, a reduced pulsatile secretion of anterior pituitary hormones and the so-called ‘wasting syndrome’ occur. The impaired pulsatile secretion of growth hormone (GH), thyrotropin and gonadotropin can be re-amplified by relevant combinations of releasing factors, which also substantially increase circulating levels of insulin-like growth factor (IGF)-I, GH-dependent IGF-binding proteins, thyroxine, tri-iodothyronine, and testosterone. Anabolism is clearly re-initiated when GH secretagogues, thyrotropin-releasing and gonadotropin-releasing hormones are co-administered but the effect on survival remains unknown. A lethal outcome of critical illness is predicted by a high serum concentration of IGF-binding protein 1, pointing to impaired insulin effect rather than pituitary function, and survival was recently shown to be dramatically improved by strict normalization of glycemia with exogenous insulin. The recent progress in the knowledge of the neuroendocrine response to critical illness and its interrelation with peripheral hormonal and metabolic alterations during stress allows for potential new therapeutic perspectives to safely reverse the wasting syndrome and improve survival. These novel insights will be reviewed herein.

Prenatal thyrotropin-releasing hormone for preterm birth.

Adding thyrotropin-releasing hormones (TRH) to corticosteroids has been suggested as a way of improving fetal lung development. The objective of this review was to assess the effect of giving prenatal TRH in addition to corticosteroids to women at risk of very preterm birth for the prevention of neonatal respiratory disease. We searched the Cochrane Pregnancy and Childbirth Group trials register, Cochrane Controlled Trials Register, and bibliographies. Date of last search: January 1999. Randomised controlled trials in women at sufficient risk of preterm birth to warrant the use of prenatal corticosteroids to promote lung maturity. TRH and corticosteroids were compared with corticosteroids with or without placebo. The main outcomes considered were fetal and neonatal mortality, neonatal morbidity, childhood development and maternal morbidity. All assessments of trial eligibility, quality and data extractions were done by at least two authors independently. Over 4500 women were recruited into the 11 included trials. Five trials were rated of high quality. Overall, prenatal TRH, in addition to corticosteroids, did not reduce the risk of neonatal respiratory disease, chronic oxygen dependance, or improve fetal, neonatal or childhood outcome in any of the outcomes assessed by intention-to-treat analyses. Indeed, the data showed prenatal TRH to have adverse effects for women and their infants. All side effects monitored were more likely to occur in women receiving TRH. In the infants, prenatal TRH increased the risk of infants needing ventilation (relative risk (RR) 1.16, 95% confidence interval (CI) 1.03-1.29), having a low Apgar score at five minutes (RR 1.80, 95% CI 1.14-1.92) and, for the one trial providing data, was associated with poorer outcomes at the 12 month follow up. Sensitivity analyses by trial quality, or subgroups with differing times from entry to delivery, or different dose regimens of TRH, did not change these findings. On the basis of currently available evidence, prenatal TRH, in addition to corticosteroids, given to women at risk of very preterm birth cannot be recommended for clinical practice.

Stress-induced inhibition of the hypothalamic-pituitary-thyroid axis is attenuated in the aged Fischer 344/N male rat.

Aging is associated with a progressive decrement in the basal activity of the hypothalamic-pituitary-thyroid axis in male Fischer 344/N rats. The aim of this study was to determine whether stress influences the activity of this axis in young and old rats. As prolactin and growth hormone share some regulatory mechanisms with thyrotropin-releasing and thyroid-stimulating hormones, which are influenced by stress, the plasma levels of these two hormones were also determined during immobilization (Immo). To accomplish this, young (3-month-old) and old (23-month-old) male 344/N Fischer rats were immobilized for 2 h; blood was collected by cannulation from the tail artery at different intervals during Immo (0, 5, 30, 60, and 120 min), and brains were removed at the end of Immo. The basal plasma levels of thyroid-stimulating hormone were similar in both groups, but were significantly and progressively inhibited by Immo in young, but not in old rats. The baseline plasma levels of total triiodothyronine were slightly lower in old than in young rats; Immo caused a significant decrease of total triiodothyronine levels only in the young animals. The baseline plasma levels of free triiodothyronine were similar and were not altered by Immo in either age group. The paraventricular nucleus thyrotropin-releasing hormone mRNA levels were lower in old than in young rats under basal conditions; under stress they were significantly inhibited in young, but remained unchanged in old rats. The basal thyroid-stimulating hormone beta mRNA levels in the anterior pituitary were significantly lower in old than in young rats, but were not affected by Immo in either age group. The plasma prolactin levels were similar at baseline and were significantly increased by Immo in both age groups, but significantly more in old than in young rats. The plasma growth hormone levels were also similar at baseline; they were significantly decreased by Immo to a similar extent in both age groups. In summary, these data indicate that the stress-induced decrease in plasma thyroid-stimulating hormone is in part mediated at the level of the hypothalamic thyrotrophin-releasing hormone neuron and that this phenomenon is attenuated in the aged rat.

Effect of Antenatal Corticosteroids and Thyrotropin-Releasing Hormones on Outcome of Surfactant-Treated Neonates

We conducted a retrospective study designed to assess the impact of antenatal combined treatment with betamethasone and TRH on preterm neonates receiving prophylactic Exosurf at birth. Of 71 neonates entered in the study, 35 received Exosurf alone and 36 were exposed prenatally to both hormones and also received Exosurf. Gestational age and birth weight were comparable in both groups (29.0 ± 2.9 weeks and 1.17 ± 0.35 kg versus 29.0 ± 3.2 weeks and 1.15 ± 0.34 kg, mean ± SD, respectively). Likewise, the proportion of neonates intubated at 72 h after birth and their ventilatory settings at that time were similar. Significant decreases of retinopathy of prematurity and death or need for mechanical ventilation at 28 days were noted in surfactant-treated neonates exposed to prenatal hormones. However, severe PIVH, PDA and need for supplemental O2 beyond 28 days after birth occurred in the same proportion of neonates from either group. Although overall mortality and air leaks occurred less frequently in neonate...

Thyrotropin and gonadotropin releasing hormones (TRH and GnRH) do not alter levels of oxytocin and oxytocin does not change the response of luteinizing or follicle stimulating hormones to GnRH in humans.

Four hundred micrograms of synthetic thyrotropin releasing hormone (TRH) were given intravenously to 4 normal men and 4 normal women, and four weeks later, 1000 micrograms of TRH were administered intravenously to 4 of the 8 individuals and oxytocin (OT) was measured in plasma on both occasions. Following injection of either dose of TRH, OT did not change significantly from baseline. Likewise, synthetic gonadotropin releasing hormone (GnRH), 100 micrograms, administered intravenously to 6 normal men did not alter the levels of OT from baseline. Synthetic OT, 300 mU/minute, administered 30 minutes before and for 90 minutes after injection of GnRH, was without effect on the GnRH-induced rise of luteinizing hormone (LH) or follicle stimulating hormone (FSH) in normal men. We conclude that continuous infusion of OT in pharmacologic concentrations does not alter the pituitary release of LH or FSH in response to GnRH in humans. TRH and GnRH given intravenously do not alter basal levels of OT in the plasma of humans, thus a physiologic role for GnRH or TRH in the neuroendocrine control of OT secretion in humans is unlikely.

Increased sensitivity of the thyrotroph to thyrotropin-releasing hormones in rats with hypothalamic hypothyroidism.

The status of TSH secretion in hypothalamic hypothyroidism was evaluated by using rats with anterior medial basal hypothalamic deafferentation as the experimental model of the disorder. In the deafferented rats, the basal serum thyroid hormone concentrations as well as that of TSH was significantly lower than normal and cold exposure failed to increase serum TSH, indicating they were in fact in a hypothalamic hypothyroid state. The minimum effective dose of TRH to elicit an increase in serum TSH was smaller in the deafferented rats than in the controls, whereas the response to the maximum dose of TRH was similar in both groups. Although the radioimmunoassayable TSH of the adenohypophysis was significantly decreased in the deafferented rats, it was qualitatively similar to that of the control rats, since the peak of TSH immunoreactivity was eluted at exactly the same position on the gel filtration column in the pituitaries from normal and deafferented rats. When the adenohypophysis was perifused in vitro with Krebs-Ringer solution buffered with Hepes, the minimum effective dose of TRH was similar in both cases. This finding suggests that the exposure to the perifusion medium completely devoid of thyroid and hypothalamic hormones erased the difference in sensitivity to TRH between the two groups as observed in vivo, although in vivo experiments on deafferented rats with normal thyroid hormone induced by exogenous thyroid hormone were not performed. Our results indicate that in hypothalamic hypothyroid rats: 1) the sensitivity but not the responsiveness of the thyrotroph to TRH is increased; and 2) the readily releasable fraction of pituitary TSH pool in response to exogenous TRH is increased. It is also suggested that the difference in the milieu between the pituitary of normal and deafferented rats in vivo is critically important for the latter to retain hypersensitivity to TRH.

Comparative studies of thyrotropin releasing hormone diazomethyl ketone and chloromethyl ketone analogs

Diazomethyl ketone and chloromethyl ketone analogs of thyrotropin releasing hormones have been synthesized and studied for their inhibitory effects on thyrotropin releasing hormone-induced release of radioactive 125I-labelled hormones from the thyroid gland of eight-week old male Long-Evans rats. When Long-Evans rats were pretreated with thyrotropin releasing hormone diazomethyl ketone (TRH-DMK) or the chloromethyl ketone derivative (TRH-CMK), a dose-related inhibition of thyrotropin releasing hormone-induced 125I release was observed which could be partially reversed by thyrotropin stimulating hormone (TSH). The diazomethyl ketone was a more effective inhibitor than the chloromethyl ketone. These compounds may act as an active-site directed antagonists whose effects are unique to the hypothalamo-pituitary-thyroid system.

Subcellular distribution of brain peptidases degrading luteinizing hormone releasing hormone (LHRH) and thyrotropin releasing hormone (TRH)

The luteinizing hormone and thyrotropin-releasing hormones have been shown to be mostly concentrated in the nerve endings of the median eminence. In contrast, the peptidases reponsible for their degradation present an ubiquitous localization and most of the reports have dealt with the total soluble activity. A detailed study of the subcellular distribution of these enzymes was thus performed in cerebral cortical and hypothalamic preparations of rat brain. The activity of a soluble marker, lactic dehydrogenase, was also measured to control for possible contaminants. The results showed that only 10% peptidase activity was present in the nerve ending preparation. Evidence is provided for a non-negligible membrane-bound enzymatic component responsible for TRH degradation at the synaptosomal level of both cortex and hypothalamus.

Substance P found to lower body temperature and aggression

Synthetic substance P (SP) was bioassayed in mice by a procedure comprising eleven subtests. Two replications of a dose-response study were conducted at the time of the peak effect of the intravenous injection of SP. Single doses of 31 and 63 ng/kg significantly decreased body temperature. SP, [D-Arg 1]-SP, and [des-NH 2-Arg 1]-SP comparably lowered blood pressure, but [D-Arg 1]-SP and [des-NH 2-Arg 1]-SP were 1 20 to 1 10 as active as SP in lowering body temperature. The activities that lower body temperature and blood pressure may be different. The thyrotropin and luteinizing hormone releasing hormones (TRH and LH-RH) did not lower body temperature. SP also decreased the aggressive response (ED 50, 89 ng/kg).

Characterization of functional receptors for somatostatin in rat pituitary cells in culture.

GH4C1 cells are a clonal strain of rat pituitary tumor cells which synthesize and secrete prolactin and growth hormone. Somatostatin, a hypothalamic tetradecapeptide, inhibits the release of growth hormone and, under certain circumstances, also prolactin from normal pituitary cells. We have prepared [125I-Tyr1]somatostatin (approximately 2200 C1/mmol) and have shown that this ligand binds to a limited number of high affinity sites on GH4C1 cells. Half-maximal binding of somatostatin occurred at a concentration of 6 x 10(-10) M. A maximum of 0.11 pmol of [125I-Tyr1]somatostatin was bound per mg of cell protein, equivalent to 13,000 receptor sites per cell. The rate constant for binding (kon) was 8 x 10(7) M(-1) min(-1). The rate constant for dissociation (koff) was determined by direct measurement to be 0.02 min(-1) both in the presence and absence of excess nonradioactive somatostatin. Binding of [125I-Tyr1]somatostatin was not inhibited by 10(-7) M thyrotropin-releasing hormones. Substance P, neurotensin, luteinizing hormone-releasing hormone, calcitonin, adrenocorticotropin, or insulin. Of seven nonpituitary cell lines tested, none had specific receptors for somatostatin. Somatostatin was shown to inhibit prolactin and growth hormone production by CH4C1 cells. The dose-response characteristics for binding and the biological actions of somatostatin were essentially coincident. Furthermore, among several clonal pituitary cell strains tested, only those which had receptors for somatostatin showed a biological response to the hormone. We conclude that the characterized somatostatin receptor is necessary for the biological actions of somatostatin on GH4C1 cells.

Localisation of gonadotropin-releasing and thyrotropin-releasing hormones in human brain by radioimmunoassay.

Localization of gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) in the human brain by radioimmunoassay is reported. The hypothalami and other brain regions were obtained during routine autopsies from 3 22-40 year old females and 12 41-95 year old males. GnRH concentration was highest in the preoptic area (340 pg/mg tissue) and declined progessively toward the caudal region which contained negligible amounts of GnRH. The highest concentrations of TRH were found in the posterior nucleus (158 pg/mg tissue) and the premammillary area. Exceedingly high concentrations of both hormones were in the pituitary stalk (1430 pg/mg and 855 pg/ml tissue for GnRH and TRH respectively). Total content of GnRH in the hypothalamus was 40.5 ng and in the pituitary stalk 58.6 ng. TRH content in the hypothalamus was 61.7 ng and in the pituitary stalk 35 ng. No apparent differences were observed in relation to age or sex. The absence of TRH in the lower 1/3rd of the pituitary stalk implies that it reaches the anterior pituitary by was of the long portal vessels whereas GnRH which is evenly distributed along the whole pituitary stalk and infundibular stem is transported via the long and short portal vessels.

Fine Structure of the Pars Distalis of the Pituitary Gland in the Female Mink,Mustela vison

Pituitary glands of intact and experimental adult females of mink, Mustela vison, were examined by electron microscopy. Conventional methods involving removal of endocrine glands (ovaries and adrenals), administration of radioactive isotope, 131I, blocking agents (thiouracil and metopirone) and hormones (thyroxine, hydrocortisone, thyrotropin and luteinizing hormone releasing hormones) were employed. Five categories of granular cells were distinguished both by their ultrastructural characteristics and qualitative changes throughout the year and following different treatments. The cell types are described and their functions discussed. From conventional electron microscopical studies it proved difficult to draw any satisfactory conclusions about the gonadotropic cells. Further investigation by means of immunocytochemistry and radioimmunoassay techniques is required to determine, whether the presumptive gonadotropic cell type produces both FSH and ICSH or only one of these hormones. Morphologically two types of agranular cells were identified. Their morphological inter-relationship and function are discussed briefly.