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Iodine Research

Resource Network of The Iodine Movement

                                     Iodine and the Body


Iodine is concentrated at high levels in the ovaries via the NIS symporter.

Iodine deficiency is strongly correlated with ovarian cysts and may also be related to ovarian cancer.

Flechas states that the greater the iodine deficiency, the more ovarian cysts a woman produces,
resulting in the extreme form known as polycystic ovarian disease.

Howenstine asserts that Iodine therapy can reduce or eliminate ovarian cysts.

Slebodzinski states that iodine concentration in the ovary is higher than in every other organs
except the thyroid. The ovarian iodide uptake varies with sexual activities, is enhanced by estrogens
and a hypothyroid state and blocked by goitrogens.

Escobar investigated the effect of various levels of iodine intake on thyroid hormones in different
tissues in the rat.  They discovered that, under conditions of iodine deficiency, the concentration of
T3 in the ovary was much higher than in the blood or most other tissues.

Distribution and fate of 131-I in the mammalian ovary.
Benstsson G, Ewaldsson B, Hansson E, Ullberg S
Acta Endocrinol (Copenh). 1963 Jan;42:122-8.
[citation only]

The distribution of radioiodide in the genital tract of the ewe.
Hovell GJ, Cullen R, Brown-Grant K.
J Reprod Fertil. 1973 Sep;34(3):535-7.
[citation only]

The sites of iodide concentration in the oviduct and the uterus of the rat.
Brown-Grant K, Rogers AW.
J Endocrinol. 1972 Jun;53(3):355-62.

Previous studies have shown that under the influence of progesterone the concentrations of
radioiodide in the uterus and oviduct of the rat are maintained at levels higher than that in the
plasma.  In the present experiments the uterus and oviducts from rats killed 2 h. after the injection of
Na-125I were autoradiographed by a technique which permits the localization of diffusible radioactive
material.  Intact non-pregnant rats and ovariectomized rats not injected with progesterone, uniformly
low grain densities were observed over sections of oviduct and uterus with the exception of the
epithelium and lumen of the oviduct where some increase in grain density was observed.  In intact
and ovariectomized rats treated with progesterone and in rats killed on Day 3 or 4 of pregnancy,
grain densities over the epithelium and lumen of the oviduct were very high but the fimbria of the
oviduct were consistently unlabelled.  The stroma underlying the oviduct epithelium was also
labelled.  In the uteri of these animals the principal site of concentration of radioiodide was the
luminal epithelium, but for technical reasons it was not possible to exclude the stroma immediately
adjacent to the luminal epithelium as a less active site of concentration of iodide.  No other site in the
uterus concentrated radioiodide.  The luminal epithelium occupies less than 3% of the volume of the
uterus in ovariectomized rats; if this tissue is taken as the sole site of iodide concentration in the
uterus, the levels reached in these cells must be at least a hundred times that of the plasma when
the overall uterus:plasma concentration ratio for radioiodide is 4 or more.

Analysis of the effects of progesterone on the synthesis of RNA and protein in the uterus of the
ovariectomized rat and on the development of an iodide concentrating mechanism.
Brown-Grant K, John PN, Rogers AW.
J Endocrinol. 1972 Jun;53(3):363-74.
[citation only]

Early effects of progesterone on the uterus of the ovariectomized rat.
Rogers AW, John PN, Brown-Grant K.
J Anat. 1970 Jan;106(Pt 1):182-3.
[citation only]

A quantitative study of the effects of progesterone and related steroids on the uterus:plasma
concentration ratio for radioactive iodide in the rat.
Brown-Grant K
J Endocrinol. 1967 Jun;38(2):145-61.
[citation only]

The effects of a single injection of progesterone on the oestrous cycle, thyroid gland activity and
uterus-plasma concentration ratio for radio-iodide in the rat.
Brown-Grant K.
J Physiol. 1967 May;190(1):101-21.

1. A single subcutaneous injection of 5 mg, 1·25 mg or 625 μg, but not 312 μg, of progesterone in oil
delayed ovulation in the rat by 1 or more days, when injected at the dioestrous stage of a 4-day
oestrous cycle.
2. When ovulation was delayed in this way the expected increase in the thyroid-serum concentration
ratio for 131I was also delayed but the ratio did increase when delayed ovulation occurred.
3. A single injection of progesterone resulted in an increase in the uterus-plasma and oviduct-plasma
concentration ratios for 131I; the increase was greatest when steroid was injected at the dioestrous
stage of the cycle and was delayed and least when the steroid was given at the pro-oestrous stage.
4. Ovulation was advanced by 1 day when progesterone was injected on the second day of dioestrus
in rats showing regular 5-day cycles; this ovulation was not accompanied by an increase in the
thyroid-serum concentration ratio. In these experiments a dose of progesterone that failed to
advance ovulation produced a rise in uterus-plasma and oviduct-plasma ratio for 131I but no rise
was seen when ovulation was induced, suggesting that oestrogen secretion had been stimulated.
5. 20α-Dihydroprogesterone (pregn-4-en-20α-o1-3-one) was not effective in delaying or advancing
ovulation at a dose level of 2·5 mg per rat and had no effect on the uterus-plasma concentration
ratio for radio-iodide.
6. These results are discussed in relation to the hypothesis that the increase in thyroid gland activity
at the oestrous stage of the cycle is related to the neuro-endocrine changes that lead to ovulation.

The sites of concentration of radioiodide in the oviduct and uterus of the ovariectomized rat, under
the influence of progesterone.
Brown-Grant K, Rogers AW
J Anat 1967.  101, pp 622-623 (Abstr)
[citation only]

Concentration of radioiodide by the uterus of the rat and the relationship to blastocyst implantation
Brown-Grant K
J Physiol. 1966 May;184(2):418-32.

1. When pregnant rats are ovariectomized early in pregnancy and treated with progesterone a raised
uterus—plasma concentration ratio (U/P ratio) for radio-iodide is observed at the usual stage of
pregnancy (days 3, 4 and 5) but is not followed by implantation. When delayed implantation is
induced by the administration of oestradiol it is not preceded by a rise in the U/P ratio for 131I.
2. Similar findings are obtained when implantation is delayed by concurrent lactation in rats mated at
the post-partum oestrus.
3. Ovariectomy early in pregnancy without progesterone treatment prevents the rise in U/P and
oviduct—plasma (O/P) ratio for 131I that normally occurs.
4. Administration of progesterone to intact or ovariectomized non-pregnant rats produces a raised
U/P and O/P ratio for 131I; oestrogen may inhibit this response. The simplest explanation of these
results is a direct action of progesterone on the uterus.
5. By gross dissection it was possible to show that the region of high iodide concentration in the rat
uterus is the endometrium.
6. No evidence of a concentration of iodide in the uterus or oviduct of the pregnant rabbit was

Mechanisms of adaptation to iodine deficiency in rats: thyroid status is tissue specific. Its relevance
for man.
Pedraza PE, Obregon MJ, Escobar-Morreale HF, del Rey FE, de Escobar GM.
Endocrinology. 2006 May;147(5):2098-108. Epub 2006 Feb 2.

As already described for the liver, lung, brain, and BAT, the patterns of change in T3 varied greatly
among these other tissues.  The greatest difference was found between the patterns for the ovary
and adrenal.  In the ovary there is a very remarkable increase of T3 in the animals on LID [Low
Iodine Diet] + 1.0 [1.0 mcg I/20g], LID + 0.5, and LID, compared with LID + 5.0, with an almost 2-fold
increase in the LID + 0.5 group.  Ovarian T3 is still higher than that of the controls, even in the LID'
[Low Iodine Diet + perchlorate]  group, in which serum T3 was decreased by about 50%.

The most unexpected and striking results are those obtained for the concentration of T3 in the ovary
and lung, where it is much higher, and in the adrenal, where it is much lower, than expected from the
normal circulating T3.

The findings in the ovary may underlie the observation that even very severely I-deficient animals
are easily mated, do not show decreased fertility, and bear litters of normal size, in contrast to Tx or
goitrogen-treated hypothyroid females.

How does iodine deficiency manifest itself?
Flechas JD

Iodine can be concentrated in the ovaries, and Russian studies done some years ago showed a
relationship between iodine deficiency and the presence of cysts in the ovaries. The greater the
iodine deficiency, the more ovarian cysts a woman produces. In its extreme form, this condition is
known as polycystic ovarian disease.

Iodine Is Vital for Good Health
Howenstine J.

Iodine therapy resolves nearly every case of breast cysts. This treatment also can heal ovarian cysts
and works well on skin cysts when rubbed over the cyst....It can help open up blocked arteries,
disinfect water, cure bladder infections, reduce or eliminate ovarian cysts.

131I uptake in a benign serous cystadenoma of the ovary.
Kim EE, Pjura G, Gobuty A, Verani R.
Eur J Nucl Med. 1984;9(9):433-5.
[abstract only]

A patient with well-differentiated thyroid carcinoma had a whole body scan using 5 mCi 131I which
demonstrated abnormal uptake of 131I in a palpable pelvic mass. Approximately 24 years ago the
patient had a total thyroidectomy followed by 131I treatment. The histologic examination of the mass
was consistent with serous cystadenoma of the ovary. No thyroid tissue or teratoma was identified.
The mechanism for the unusual uptake of 131I in a benign ovarian tumor is not clear, and the
differential diagnosis of metastatic thyroid cancer is briefly reviewed.

Multicystic ovaries in primary hypothyroidism.
Lindsay AN, Voorhess ML, MacGillivray MH.
Obstet Gynecol. 1983 Apr;61(4):433-7.
[abstract only]

Nine of 12 girls diagnosed consecutively as having severe and longstanding primary hypothyroidism
were found to have multicystic ovaries when evaluated by pelvic ultrasound examination. The cysts
resolved rapidly with thyroid replacement therapy. The patients had either elevated or high normal
plasma luteinizing hormone levels which decreased markedly after thyroid therapy. Five of seven
patients tested with luteinizing hormone-releasing hormone had attenuated gonadotropin responses;
the other two reacted normally. The pathogenesis of the cysts remains uncertain. Use of pelvic
ultrasound scan has documented a high frequency of multicystic ovaries in girls with primary

Abnormal iodine-131 uptake in a benign mucinous ovarian cystadenoma mimicking struma ovarii.
Morel O, Rohmer V, Girault S, Muratet JP, Berthelot C, Jallet P.
Clin Nucl Med. 2007 Jan;32(1):64-6.
[citation only]

Hormonal regulation of iodine accumulation in ovary and thyroid of Japanese quail.
Newcomer WS.
Gen Comp Endocrinol. 1982 Jun;47(2):243-8.
[citation only]

Ovarian iodide uptake and triiodothyronine generation in follicular fluid. The enigma of the thyroid
ovary interaction.
Slebodzinski AB.
Domest Anim Endocrinol. 2005 Jul;29(1):97-103. Epub 2005 Apr 7. Review.

Since 1928, the iodine concentration in the ovary has been known to be higher than in every other
organs except the thyroid. The ovarian iodide uptake varies with sexual activities, is enhanced by
estrogens and a hypothyroid state and blocked by goitrogens. The recent discovery of a sodium
iodide symporter (NIS) in ovaries has offered a possible mechanism for ovarian iodide uptake and
other functional similarities to its thyroid counterpart. Nevertheless, the physiological significance of
ovarian iodine uptake and accumulation remains unknown. The presence of thyroid hormones (TH)
in follicular fluid (FF) has been established recently. Our preliminary studies on TH in FF (1996-
1998) in rabbits, pigs, horses showed that the concentration of T4 is generally lower than that in
serum and that for T3 is within the normal range or higher. A positive correlation exists between the
T4 levels in FF and serum but not between the corresponding T3 levels. These studies revealed, for
the first time, the presence of the ovarian 5'-monodeiodinase system in FF capable of generating T3
(ovary-born T3) by outer ring deiodination of T4. In mares, seasonal polyestrus, ovarian 5'-
monodeiodinase (MD) activity and FF T3 levels have been found to be higher during the ovulatory
period than in the anovulatory one. The exact physiological significance of this system generating T3
and coexisting with isoforms of TH receptors in granulosa cells has not been elucidated. A direct role
of T3 for the early follicular development, differentiation and for the steroidogenic capability of
granulosa cells, although strongly suggested by data obtained from in vitro studies, has to be

Observations on the influence of stilboestrol on iodine economy of the body in intact guinea pigs.
Slebodzinski A
Acta Med Pol. 1963;4:399-409.
[citation only]

Expression of multiple thyroid hormone receptor mRNAs in human oocytes, cumulus cells, and
granulosa cells.
Zhang SS, Carrillo AJ, Darling DS.
Mol Hum Reprod. 1997 Jul;3(7):555-62.

Thyroid hormones have diverse effects on ovarian function. We examined the expression of thyroid
hormone receptor (TR) mRNAs (including TRalpha-1, TRbeta-1, TRbeta-2, and c-erbAalpha-2
isoforms) in three types of cells from human follicles, and determined the concentration of free tri-
iodothyronine (T3) present in human follicular fluid. Human failed-fertilized oocytes, granulosa (GC)
and cumulus (CC) cells from patients of the in-vitro fertilization (IVF) programme at Alliant Hospital
Fertility Center were used to detect TR mRNA expression using reverse transcription-polymerase
chain reaction (RT-PCR) followed by Southern blot analysis. Human spermatozoa were also
analysed to determine whether results obtained with CC would be affected by the presence of
spermatozoa. beta-Actin mRNA was amplified in each cell type as a positive control for the RT-PCR.
Our results show that human oocytes express TRalpha-1, TRbeta-1, TRbeta-2, and c-erbAalpha-2
mRNAs and that these same isoforms are expressed in both human granulosa cells and cumulus
cells. No differences were detected in the apparent amounts of RT-PCR products when comparing
GC with CC, suggesting a similar pattern of expression of these RNAs. beta-actin mRNA was
detected in spermatozoa, but TRalpha-1 expression was not detectable. The concentrations of free
T3 measured in follicular fluid were similar to, or slightly below, those in serum of euthyroid patients.
These data demonstrated that several isoforms of TR mRNA are expressed in the human oocyte,
and hence thyroid hormone may have direct affects on the oocyte, as well as on GC and CC. In
addition thyroid hormone may have indirect effects on the oocytes via the CC.


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