Relationship between mild iodine deficiency in pregnant women and thyroid function: A meta-analysis

BackgroundPregnant women are among the key groups in iodine nutrition evaluation. The purpose of the present study was to summarize the evidence supporting the relationship between mild iodine deficiency (UIC: 100–150 μg/L) in pregnant women and levels of thyroid function tests.MethodsThis review follows the guidelines for systematic reviews (PRISMA 2020). Three electronic databases (PubMed, Medline, and Embase) were searched for relevant publications in English on the association between mild iodine deficiency in pregnant women and thyroid function. Articles published in Chinese were searched in China’s electronic databases (CNKI, WanFang, CBM, and WeiPu). Pooled effects were presented as standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) using fixed or random effect models, respectively. This meta-analysis was registered at www.crd.york.ac.uk/prospero as CRD42019128120.ResultsWe summarized the results from 7 articles with 8261 participants. The overall pooled results showed that the levels of FT₃, FT4, and abnormal TgAb (the antibody levels exceeded the upper limit of the reference range) were significantly increased in pregnant women with mild iodine deficiency compared to pregnant women with adequate iodine status (FT₃: SMD=0.854, 95% CI: 0.188, 1.520; FT₄: SMD=0.550, 95% CI: 0.050, 1.051; TgAb: OR=1.292, 95% CI: 1.095; 1.524). Subgroup analysis was carried out on the sample size, ethnicity, country, and gestation of FT₃, FT_4, and TSH, but no plausible factor was found. Egger’s tests indicated no publication bias.The increase in FT₃ and FT_4, as well as TgAb levels, in pregnant women is associated with mild iodine deficiency.ConclusionMild iodine deficiency is associated with an increase in FT_3,FT₄ and TgAb levels in pregnant women. Mild iodine deficiency may increase the risk of thyroid dysfunction in pregnant women.     

Excessive iodine intake and thyroid dysfunction among lactating Saharawi women

ObjectivesExcessive iodine intake may lead to thyroid dysfunction, which may be particularly harmful during pregnancy and lactation. The main objective was to describe iodine status and the prevalence of thyroid dysfunction among lactating women in areas with high iodine (HI) and very high iodine (VHI) concentrations in drinking water.Design and methodsA cross-sectional survey was performed among 111 lactating women in the Saharawi refugee camps, Algeria. Breast milk iodine concentration (BMIC), urinary iodine concentration (UIC) and the iodine concentration in the most commonly consumed foods/drinks were measured. A 24-h dietary recall was used to estimate iodine intake. Thyroid hormones and antibodies were measured in serum.ResultsMedian UIC, BMIC and iodine intake across both areas was 350 μg/L, 479 μg/L and 407 μg/day, respectively. In multiple regression analyses, we discovered that being from VHI area was associated with higher UIC and BMIC. BMIC was also positively associated with iodine intake. Thyroid dysfunction and/or positive thyroid antibodies were found in 33.3% of the women, of which 18.9% had hypothyroidism and 8.1% had hyperthyroidism and 6.3% had positive antibodies with normal thyroid function. Elevated thyroid antibodies were in total found in 17.1%. We found no difference in distribution of thyroid dysfunction or positive antibodies between HI and VHI areas. BMI, BMIC and elevated thyroglobulin (Tg) predicted abnormal thyroid function tests.ConclusionsThe high prevalence of thyroid dysfunction may be caused by excessive iodine intake over several years.     

Exploring the role of copper and selenium in the maintenance of normal thyroid function among healthy Koreans

BackgroundSelenium and iodine are trace elements well known to have important roles in the synthesis and metabolism of thyroid hormones. However, the effects of other trace elements on thyroid hormones are still inconclusive. We investigated the association between several trace elements and thyroid hormones.MethodsThe data of 448 subjects who were measured for both, trace elements and TSH/free T4, at the Heath Checkup Center were retrospectively reviewed. The presence of thyroiditis (from thyroid echogenicity) and thyroid nodules were reviewed in the subjects who underwent thyroid ultrasonography.ResultsBlood concentrations of manganese, copper, selenium, and molybdenum were associated with TSH or free T4. After adjusting for age, sex, BMI, smoking, and alcohol consumption, blood copper levels were positively associated with free T4 in both sexes and selenium levels were positively associated with free T4 in women. There was no association between trace elements and thyroiditis. Blood copper concentration had a weak non-linear association with the presence of thyroid nodules.ConclusionsThis study demonstrated that blood concentrations of copper and selenium were significantly associated with free T4 in healthy Korean subjects with sufficient iodine intake suggesting their role in maintaining normal thyroid function.     

Iodine status in Danish pregnant and breastfeeding women including studies of some challenges in urinary iodine status evaluation

Denmark was previously iodine deficient with regional differences. Moderate iodine deficiency appeared in West Denmark and mild iodine deficiency in East Denmark and also Danish pregnant and breastfeeding women suffered from iodine deficiency. The Danish mandatory iodine fortification of salt was introduced in the year 2000 and has increased iodine intake in the Danish population. However, median urinary iodine concentration in the general population and in pregnant and breastfeeding women is still below the level recommended, corresponding to mild iodine deficiency. Certain characteristics may challenge the evaluation of urinary iodine status in pregnancy and during breastfeeding. This review also addresses methodological challenges related to spot urine sampling conditions and the use of iodine supplement and discusses the use of non-pregnant population groups as a proxy for iodine intake in pregnant women.     

Development of thyroid dysfunction among women with excessive iodine intake – A 3-year follow-up

ObjectivesThyroid dysfunction can be a result of excessive iodine intake, which may have adverse health consequences, particularly for women in fertile age. In 2010, we conducted a cross-sectional study among lactating women with excessive iodine intake in the Saharawi refugee camps in Algeria and found a high prevalence of thyroid dysfunction. Three years later, we conducted a follow-up study to monitor the iodine situation and explore whether thyroid dysfunction still was highly prevalent when the women no longer were post-partum. None of the women were treated for hyper- or hypothyroidism between baseline and follow-up.MethodsIn 2013, we were able to recapture 78 of the 111 women from the baseline. Thyroid hormones and antibodies were measured in serum and thyroid size was assessed by palpation. Urinary iodine concentration (UIC) and drinking water iodine concentration were measured.ResultsThe overall prevalence of thyroid dysfunction and/or positive antibodies was 34.3% and was not significantly changed from baseline. Of the non-pregnant women we reexamined, 17 had hypo- or hyperthyroidism in 2010; among these, 12 women still had abnormal thyroid function at follow-up. In addition, we found 9 new cases with marginally abnormal thyroid function. Women with thyroid dysfunction and/or positive antibodies had significantly higher BMI and thyroglobulin than women with normal thyroid function. We also found that women with high breast milk iodine concentration (BMIC) at baseline had more thyroid dysfunction at follow-up than the women with lower BMIC at baseline.ConclusionsAt follow-up, the prevalence of thyroid dysfunction was still high and had not changed during the 3 years between studies and from a postpartum period. The women still had a high iodine intake indicated by high UIC. Breast milk iodine concentration from baseline predicted thyroid dysfunction at follow-up.     

Effect of aging on the morphology and function of the thyroid gland of the cream hamster

Summary The effect of aging on the morphology and function of the thyroid gland of the cream hamster was studied by light and electron microscopy coupled with autoradiography or histochemistry.Morphologically, aging induces an accumulation of lysosomal dense bodies and a loss of the phagocytosis of colloid droplets after stimulation with TSH. Iodine uptake and organification occur normally and thyroglobulin synthesis, estimated by autoradiography with ³H-leucine, is not different from that observed in young animals. The basal T₄ and T₃ plasma levels are lower in the old animals. A low iodine diet administered for several months prevents the age related accumulation of lysosomal dense bodies. Hormone secretion seems to proceed by two different mechanisms; phagocytosis of colloid droplets, the classical mechanism that decreases with age, and an additional mechanism, probably micropinocytosis, that is maintained during the whole lifespan.Presented at the First French Congress of Endocrinology, Montpellier, September 1980Work was performed under contracts n 3.4523.79 and n 3.4512.80 of the Fonds de la Recherche Scientifique Médicale, thanks to a grant of the Ministère Belge de la Politique Scientifique (Action concertée) and with the help of the Fondation Interuniversitaire pour la Recherche du Processus du Vieillissement, Belgium     

Selenium,zinc, and thyroid hormones in healthy subjects

Iodothyronine 5′ deiodinase, which is mainly responsible for peripheral T₃ production, has recently been demonstrated to be a selenium (Se)-containing enzyme. The structure of nuclear thyroid hormone receptors contains Zinc (Zn) ions, crucial for the functional properties of the protein. In the elderly, reduced peripheral conversion of T₄ to T₃ with a lower T₃/T₄ ratio and overt hypothyroidism are frequently observed. We measured serum Se and RBC GSH-Px (as indices of Se status), circulating and RBC Zinc (as indices of Zn status), thyroid hormones and TSH in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to avoid abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid under- or malnutrition conditions, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. Low T₃/T₄ ratios and reduced Se and RBC GSH-Px activity were observed only in the older group. A highly significant linear correlation between the T₃/T₄ ratio and indices of Se status was observed in the older group of subjects (r=0.54;p<0.002, for Se;r=0.50;p<0.002, for RBC GSH-Px). Indices of Zn status did not correlate with thyroid hormones, but RBC Zn was decreased in older as compared with younger subjects. We concluded that reduced peripheral T₄ conversion is related to impaired Se status in the elderly.     

Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects

BackgroundThis study tested the hypothesis that abnormal maternal metabolism of both homocysteine and thyroid hormone network in pregnant women is associated with neural tube defects (NTDs) in a part of China with high NTD prevalence.MethodsA case–control study was performed between 2007 and 2009 in Lüliang Mountains, Shanxi Province. This study included 83 pregnant women who had fetuses with NTDs (cases) and 90 pregnant women with normal fetuses (controls). In addition, a cell model to illustrate the epidemiological findings was established.ResultsFetuses of mother who had both high total homocysteine (tHcy) and inadequate free thyroxine were 3 times more at risk of developing NTDs (adjusted odds ratio = 3.5; 95 % confidence interval = 1.2–10.4; cases vs. controls) using multivariate logistic regression models. Furthermore, biological interaction between metabolisms of Hcy and thyroid hormones was demonstrated in vitro. In homocysteine thiolactone of a metabolite of Hcy-treated mouse embryonic neural stem NE4C cells, genes (Bmp7, Ctnnb1, Notch 1, Gli2, and Rxra) related to both neural tube closure and thyroid hormone network were shown to be regulated by H3K79 homocysteinylation, which increased their expression levels.ConclusionsThe effect of maternal serum high tHcy on risk of developing NTDs is depended on maternal serum level of thyroxine. Meanwhile, a higher level of tHcy might also affect both maternal metabolism of thyroid hormone and neural tube closure in embryogenesis through homocysteinylation of histones.     

Forskolin stimulates adenylate cyclase and iodine metabolism in thyroid

Forskolin is a potent activator of the cyclic AMP-generating system in many tissues. In dog thyroid slices, the enhancement of cyclic AMP level was rapid, sustained in the presence of forskolin, but easily reversible after its withdrawal. Contrary to TSH, forskolin induced little apparent desensitization. Forskolin potentiated the effects of TSH, PGE1 and cholera toxin. However, the forskolin-induced cyclic AMP accumulation was still sensitive to inhibitors of dog thyroid adenylate cyclase such as iodide, norepinephrine and adenosine. As fluoride, but contrary to TSH and PGE1, forskolin stimulated adenylate cyclase in a medium where Mg2+ was replaced by Mn2+. This suggests that in thyroid, as in other tissues, forskolin acts beyond the receptor level but, as it potentiates hormone action and does not impair modulation by inhibitors, it may interact with the nucleotide-binding regulatory proteins. Forskolin mimicked the effect of TSH on iodide organification and secretion.     

Body dimensions and thyroid hormone levels in premenopausal and postmenopausal women from Austria

Correlations between thyroid hormone levels and body dimensions were investigated in a group of 124 premenopausal (ages 16–40 years) and 142 postmenopausal (ages 38–61 years) women from Vienna, Austria. Twenty-nine absolute body dimensions and thirteen anthropometric indices were correlated with the serum levels of thyroxine, triiodothyronine, thyroid-stimulating hormone, and thyroid-hormone-binding globulin as well as three hormone ratios (T3/T4, T4/TSH, T3/TSH). All hormones exhibited statistically significant correlations with 24 anthropometric variables and 11 indices. The correlations between thyroxine and triiodothyronine levels and the body measurements were predominantly positive in both proband groups. Higher thyroid hormone levels were associated positively with body dimensions, especially with the amount of subcutaneous fat tissue, in adult females independently of their menstrual status. The direction of the correlations between thyroid-stimulating hormone and body measures as well as anthropometric indices differed between the premenopausal and the postmenopausal women. While in premenopausal women mainly positive correlations between anthropometric characters and the level of thyroid stimulating hormone occur, in postmenopausal women most of these correlations are negative. This is probably due to the decrease of thyroid-stimulating hormone levels with increasing age, as well as with changes in body shape during the climacteric and after the menopause. © 1994 Wiley-Liss, Inc.     

Effects of repeated whole-body cold exposures on serum concentrations of growth hormone, thyrotropin, prolactin and thyroid hormones in healthy women

Cold therapy is used to relieve pain and inflammatory symptoms. Humoral changes may account for the pain alleviation related to the cold exposures. The aim of the present study was to examine the effects of two types of cold therapy, winter swimming in ice-cold water (WS) and whole body cryotherapy (WBC), on the serum levels of the growth hormone, prolactin, thyrotropin and free fractions of thyroid hormones (fT3, fT4). One group of healthy females (n = 6) was exposed to WS (water 0–2 °C) for 20 s and another group (n = 6) to WBC (air −110 °C) for 2 min, three times a week for 12 weeks. Blood samples used for the hormone measurements were taken on weeks 1, 4 and 12 before and 35 min after the cold exposures and on the days of the respective weeks, when the cold exposures were not performed. During the WS treatments, serum thyrotropin increased significantly at 35 min on weeks 1 (p < 0.01) and 4 (p < 0.05), but the responses were within the health-related reference interval. During the WS, the serum prolactin measured at 35 min on week 12 was lower than during the control treatment, and no changes in fT3 or fT4 were observed. During the WBC, no changes in the serum levels of the studied hormones were observed during the 12 weeks. In conclusion, repeated WS and WBC treatments for healthy females do not lead to disorders related to altered secretions of the growth hormone, prolactin, thyrotropin, or thyroid hormones.     

Structural and functional aspects of thyroid peroxidase

Thyroperoxidase (TPO) is the enzyme involved in thyroid hormone synthesis. Although many studies have been carried out on TPO since it was first identified as being the thyroid microsomal antigen involved in autoimmune thyroid disease, previous authors have focused more on the immunological than on the biochemical aspects of TPO during the last few years. Here, we review the latest contributions in the field of TPO research and provide a large reference list of original publications. Given this promising background, scientists and clinicians will certainly continue in the future to investigate the mechanisms whereby TPO contributes to hormone synthesis and constitutes an important autoantigen involved in autoimmune thyroid disease, and the circumstances under which the normal physiological function of this enzyme takes on a pathological role.     

Effect of serum estradiol and leptin levels on thyroid function, food intake and body weight gain in female Wistar rats

We evaluated the interplay among estrogen, leptin and thyroid function in the regulation of body mass in female rats. Adult female rats were divided into four groups: control (C, sham-operated), ovariectomized (OVX), ovariectomized treated with estradiol benzoate (Eb) 0.7 or 14 μg/100 g bw per day, during 21 days. OVX led to an increase in body mass, food intake and food efficiency (change in body mass as function of the amount of food ingested) which were normalized by the lower Eb dose, and decreased significantly when the higher dose was given. Serum leptin levels were increased more than two-fold in all ovariectomized groups. Serum T4 levels of the Eb treated OVX were significantly lower than in the controls. Serum T3 and TSH were unaffected by OVX or by Eb treatment. Uterine type 2 iodothyronine deiodinase (D2) activity changed in parallel with serum estradiol: decreased after OVX, returned to control levels after the lower E2 treatment, and increased significantly after the high Eb dosage. The hypothalamic D2 activity was reduced around 30% in all castrated groups, treated or not with estrogen, whereas in the brown adipose tissue the enzyme was not changed. Interestingly, although estrogen-treated OVX rats had lower body weight, serum leptin was high, suggesting that estrogen increases leptin secretion. Our results show that estradiol is necessary for the hypothalamic action of leptin, since the increase in leptin levels observed in all ovariectomized rats was associated with a decrease in food intake and food efficiency only in the rats treated with estrogen.     

Environmental physiology of the teleostean thyroid gland: a review

Synopsis Recent studies of thyroid hormone function are reviewed as they relate to the environmental physiology of teleost fish. In addition, reports dealing with the apparent interdependence of thyroid gland function with that of other endocrine glands are discussed with emphasis on the interrelated endocrine response associated with changing physiological status of teleosts.Seasonal changes in thyroid gland activity are described in several species. Although seasonal alterations in apparent thyroid status are concomitant with changes in ambient temperature, photoperiod and/or gonadal status, their biological significance is not fully understood and direct relationships are for the most part, not proven. Similarly, most reports of thyroid involvement in gonadal development or maturation are based on indirect evidence of the relationship. The exception to this is a study in immature or hypophysectomized goldfish in which thyroxine (T₄) was shown to promote ovarian development and maturation, possibly acting collateralistically or synergistically with gonadotropin. Even in this study it is not clear whether the T₄ effect is a direct action on the ovarian tissue or an indirect action via the regulation of metabolites necessary for gonad metabolism. Integumentary silvering and retinal porphyropsin formation in salmonids are stimulated by administration of T₄ or thyroid extracts. Administration of T₄ or triiodothyronine (T₃) enhances skeletal and somatic growth in some teleostean species, although the effect on somatic growth is most pronounced when these hormones act synergistically with somatotropin (STH) or androgens. The growth-promoting effects of T₄ and T₃ may be linked to their apparent involvement in lipid, carbohydrate, protein and vitamin metabolism. alterations in apparent thyroid activity concomitant with changes in ambient temperature have been reported (for example correlated with seasonal ambient thermal changes), although there are marked contradictions in data presented by different investigators. Reported temperature-related effects on thyroid function are probably secondary responses of thyroid metabolism to altered temperatures. Evidence of a direct rate of thyroid hormones in the regulation of migration (and associated behavioural modifications), salmonid smoltification, oxygen consumption, and osmotic or ionic regulation although highly suggestive in a number of areas is inconclusive and requires further critical experimental evaluation.The pituitary control (by thyrotropin) of thyroid secretion of T₄ is convincingly shown in several teleosts, and evidence of an inhibitory hypothalamic control of thyrotrop activity is highly suggestive in some species. A thyrotropic effect of somatotropin preparations is well established in several teleostean species; the effect does not appear to be related to contamination of the somatotropin preparations with thyrotropin, and may be an important consideration in explaining the apparently related involvement of T₄ (or T₃) and somatotropin in growth and metabolism. The apparent thyrotropic property of some gonadotropin preparations, shown in several teleostean species, requires further investigation before the doubts regarding hormone preparation purity can be satisfied. Recent studies of effects of prolactin on thyroid function are highly suggestive of an inhibitory role of prolactin in peripheral monodeiodination of T₄ to T₃ which secondarily affects thyroid activity in some species. There is no evidence of a direct involvement of corticotropin, melanotropin or fractions of these molecules on thyroid function in teleosts. Moreover, the little evidence in support of a role of gonadal or adrenocortical steroids in thyroid control is either often contradictory or indirect and needs to be evaluated further.Interlake epizootiological studies of thyroid dysfunction in Great Lakes salmonids provide substantive evidence for the presence of a ubiquitous waterborne goitrogen(s) in the Great Lakes environs. The nature of the goitrogen(s), whether naturally-occurring or a man-introduced toxicant, remains to be determined but the possible existence of waterborne goitrogens in natural water systems and their possible effects on experimental studies of teleostean thyroid function have to be evaluated further. If goitrogens are a common component of aquatic environments their presence could explain some of the data discrepancy among different groups of investigators, and could account for some of the apparent seasonal change in teleost thyroid physiology.     

Thytropin increases the iodine content of rat circulating thyroglobulin as measured by equilibrium density gradient centrifugation

In previous work we demonstrated that circulating thyroglobulin contains very little or no iodine. We have now characterized circulating thyroglobulin following administration of thyrotropin (TSH) to determine whether its iodine content remains low or increases after stimulation. The iodine content of circulating thyroglobulin was estimated from its density determined by equilibrium density gradient (isopycnic) centrifugation. TSH stimulated thyroglobulin from 182 ± 28 ng/ml to 571 ± 83 ng/ml at 8–14 h. Circulating thyroglobulin in the basal state had a density consistent with very little or no iodine. Its density increased following TSH to a maximum at 8–14 h which was nearly the same as the density of thyroglobulin extracted directly from the thyroid. To determine whether selective peripheral metabolism, based on the degree of iodination, could account for the density shift, purified rat thyroid thyroglobulin was injected into thyroidectomized rats. The density of thyroglobulin remained unchanged for 25 h during which time it was metabolized by more than 97%. Therefore, selective metabolism of thyroglobulin based on iodine content did not occur. We conclude that TSH causes a marked increase in the iodine content of circulating thyroglobulin. It is most likely that in the basal state circulating thyroglobulin comes from selective release of poorly iodinated molecules, while after TSH, it comes from release of previously synthesized, iodinated and stored molecules.     

Contribution of milk to iodine intake in France

A survey based on 838, samples of milk obtained from 537 dairies covering 70 of 95 districts in France was organized to assess iodine content of milk and its contribution to total intake. Iodine levels were significantly higher in winter than in summer. Very low iodine contents (<25 μg I/kg) were found in the eastern part of the country (the Vosges, Jura, and the Alpes) and the Massif Central. During milk processing, much of the iodine is lost in the whey. The other significant sources of dietary iodine are fish and eggs. Iodized salt is sold only to households and not to industry. Even if about 20% of the iodine is lost over the first 3 mo, salt remains the main source for this trace element. It is concluded that, if iodized salt is not provided systematically for both domestic and agro-industrial use, then milk may be the most important source of iodine. This key role may explain seasonal and geographical variations in the frequencies of goiter in France.     

Histological and ultrastructural alterations of rat thyroid gland after short-term treatment with high doses of thyroid hormones

The aim of the present study was to investigate histological alterations of rat thyroid gland after short-term treatment with supraphysiological doses of thyroid hormones. Rats from experimental groups were treated with triiodothyronine (T3) or thyroxine (T4) during five days. In both treated groups, thyrocyte height was reduced and follicular lumens were distended. Progressive involutive changes of the thyroid parenchyma were apparent, including follicular remodeling (fusion) and death of thyrocytes. Morphological changes confirmed by quantitative analysis were more pronounced in the T4-treated group. Our results demonstrate that thyrotoxicosis, whether induced by T3 or T4, leads to different grades of thyroid tissue injury, including some irreversible damages. These changes might be explained at least in part by lack of trophic and cytoprotective effects of the thyroid stimulating hormone. Since the period required for morphophysiological recovery may be unpredictable, findings presented here should be taken into consideration in cases where the thyroid hormones are used as a treatment for thyroid and non-thyroid related conditions.     

Localization of cells producing thyroid stimulating hormone in the pituitary gland of the domestic drake

Summary Cells binding anti-bovine TSH serum were found exclusively in the rostral lobe of the adenohypophysis of the drake using the peroxidase-antiperoxidase complex unlabelled antibody method. The specificity of the binding of the anti-serum to TSH cells was established by relating the morphology and relative abundance of immunochemically stained cells to the TSH content of the adenohypophysis after experimentally altering the activity of the pituitary-thyroid axis. The TSH activity of the adenohypophysis was assessed indirectly, by the weight of the thyroid glands, and directly, by bioassay. As determined by bioassay, the TSH content of the rostral lobe of the adenohypohysis was much greater than that of the caudal lobe. Compared with control drakes, immunochemically stained cells in birds fed a goitrogen, methimazole, seemed to be enlarged and were closer together, while the stained cells in drakes injected with thyroxine were shrunken and less intensely stained. The TSH content of the adenohypophysis was increased in drakes fed methimazole. Castration did not alter the TSH content of the adenohypophysis or change the morphology of immunochemically stained cells. These observations suggest that in the drake: 1) anti-bovine TSH serum binds specifically to TSH cells; 2) the TSH cells occur in the rostral and not in the caudal lobe of the adenohypophysis; and 3) the activity of TSH cells is not inhibited by the feedback effects of gonadal steroids.We thank Dr. L.E. Reichert Jr. and the National Institute of Arthritis, Metabolic and Digestive Diseases for the gift of ovine TSH and Mr. R. Wilkie for technical assistance. We are grateful to Dr. M.F. El Etreby, Professor B.K. Follett, Dr. C.G. Scanes, Dr. J. Seth and Dr. J.G. Pierce for gifts of immunochemicals