Postpartum Lactation Research Articles

Developmental stage determines the effects of MYC in the mammary epithelium

Epidemiological findings suggest that the consequences of a given oncogenic stimulus vary depending upon the developmental state of the target tissue at the time of exposure. This is particularly evident in the mammary gland, where both age at exposure to a carcinogenic stimulus and the timing of a first full-term pregnancy can markedly alter the risk of developing breast cancer. Analogous to this, the biological consequences of activating oncogenes, such as MYC, can be influenced by cellular context both in terms of cell lineage and cellular environment. In light of this, we hypothesized that the consequences of aberrant MYC activation in the mammary gland might be determined by the developmental state of the gland at the time of MYC exposure. To test this hypothesis directly, we have used a doxycycline-inducible transgenic mouse model to overexpress MYC during different stages of mammary gland development. Using this model, we find that the ability of MYC to inhibit postpartum lactation is due entirely to its activation within a specific 72-hour window during mid-pregnancy; by contrast, MYC activation either prior to or following this 72-hour window has little or no effect on postpartum lactation. Surprisingly, we find that MYC does not block postpartum lactation by inhibiting mammary epithelial differentiation, but rather by promoting differentiation and precocious lactation during pregnancy, which in turn leads to premature involution of the gland. We further show that this developmental stage-specific ability of MYC to promote mammary epithelial differentiation is tightly linked to its ability to downregulate caveolin 1 and activate Stat5 in a developmental stage-specific manner. Our findings provide unique in vivo molecular evidence for developmental stage-specific effects of oncogene activation, as well as the first evidence linking MYC with activation of the Jak2-Stat5 signaling pathway.

Change of Diurnal Heart Rate Patterns During Pregnancy and Lactation in Dogs (Canis familiaris)

Pregnancy and lactation involve great demands on the cardiovascular system. The purpose of this study was to investigate how the heart rate and diurnal heart rate pattern change when dogs become pregnant or lactate. Five clinically healthy female beagle dogs were mated, and delivered three to seven healthy puppies. The heart rate was investigated with 24-h ECG (Holter) once during anoestrus, at 3, 5, 7 and 9 weeks of pregnancy, and at week 4 postpartum (lactation). However, at 9 weeks, the ECG could not be recorded for the fully 24 h in 4 of 5 dogs, because labour started and the dogs then appeared disturbed by the recordings. The results at this date are not included in the statistical comparison. The heart rate increased progressively during pregnancy and was still elevated at 4 weeks of lactation. During late pregnancy the difference in heart rates between daytime and nighttime became smaller, but the heart rate was significantly higher in daytime in all periods. In conclusion, the increased heart rates during pregnancy and lactation reflect increased demands on the cardiovascular system and may be important to consider in clinical practice.

Sheehan's syndrome.

Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. It may be rarely seen without massive bleeding or after normal delivery. Improvement in obstetric care and availability of rapid blood transfusion coincided with a remarkable reduction in the frequency of Sheehan's syndrome particularly in western society. But it has recently been reported more often from well-developed countries. It is one of the most common causes of hypopituitarism in underdeveloped or developing countries. Enlargement of pituitary gland, small sella size, disseminated intravascular coagulation and autoimmunity have been suggested to play a role in the pathogenesis of Sheehan's syndrome in women who suffer from severe postpartum hemorrhage. The patients may seek medical advice because of various presentations ranging from non-specific symptoms to coma and the clinical manifestation may change from one patient to another. Failure of postpartum lactation and failure to resume menses after delivery are the most common presenting symptoms. Although a small percentage of patients with Sheehan's syndrome may cause abrupt onset severe hypopituitarism immediately after delivery, most patients have a mild disease and go undiagnosed and untreated for a long time. It may result in partial or panhypopituitarism and GH is one of the hormones lost earliest. The great majority of the patients has empty sella on CT or MRI. Lymphocytic hypophysitis should be kept in mind in differential diagnosis. In this review, the old and recent data regarding Sheehan's syndrome are presented.

Questioning the Cardioprotective Effect of Bromocriptine Treatment

To the Editor: I read with interest the paper “Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance” by Drs Franchi, Lazzeri, Barletta, Ianni, and Mannelli, which was published in July 2001.1 The authors cite a report by Przuntek et al2 published in 1992 that suggested that bromocriptine treatment lessened mortality in patients with Parkinson disease. The authors presumed that this putative cardioprotective effect can be related to withdrawal of cardiac sympathetic activity leading to fewer life-threatening ventricular arrhythmias. Unfortunately, the authors failed to mention that since 1992, long-term studies in Australia3 and France4 have failed to replicate the findings cited in the Przuntek paper. The Australian and French studies were of 10-year durations and found no evidence of a cardioprotective effect from bromocriptine. Over the past 25 years, bromocriptine has been studied in the treatment of clinical indications such as acromegaly, hyperprolactinemia, postpartum lactation suppression, cocaine craving, and diabetes mellitus, in addition to Parkinson disease. Rather than a cardioprotective effect, bromocriptine shares with other ergot alkaloids the property of vasoconstriction, with the potential for serious tissue injury. Hypertension5 and cardiac injury6 have been reported in association with bromocriptine use in lactation suppression. Seizures and myocardial infarction were reported in association with bromocriptine use in the treatment of cocaine craving, which led the Italian Health Ministry to request the withdrawal of bromocriptine for use in cocaine craving.7 Finally, in clinical trials of bromocriptine for the treatment of Type 2 diabetes presented to the Food and Drug Administration, a relative risk of myocardial infarction of 2.9 after bromocriptine treatment was found.8 In the design of the study by Franchi and colleagues, the investigators used single oral doses of bromocriptine with measurements at baseline and 180 minutes after bromocriptine administration. It has long been …

Calcium Fractional Absorption and Metabolism Assessed Using Stable Isotopes Differ between Postpartum and Never Pregnant Women

Determining the fractional absorption (FA) of calcium using the incorporation into urine of stable isotopes given intravenously (IV) and orally has become a routine procedure. We investigated the FA of calcium in two groups of (2-3 mo) postpartum women lactating (LACT) (n = 6) and nonlactating (PPNL) (n = 6), and in never pregnant (NP) women (n = 7). The women consumed a controlled diet containing 30-33 mmol/d calcium (Ca) for 21 d. On d 7 of the controlled diet, the women received 0.05 mmol of 42Ca IV and 0.25 mmol 44Ca orally in milk. Urine samples (24-h) were collected for the next 14 d and morning blood samples were collected from fasting subjects before dosing and at 24 and 48 h after receiving the isotopes. Milk samples from the LACT women were collected from each feeding beginning 24 h before to 72 h after dosing. There were no significant differences in the FA of calcium as measured by stable isotope incorporation into urine (23.8 +/- 2.9%), serum (24.0 +/- 3.4%) or milk (23.6 +/- 3.6%) of LACT women. The fractional calcium absorption measured in urine of the postpartum women (LACT and PPNL, 23.8 +/- 2.9% and 25.0 +/- 3.3%, respectively) did not differ but was greater (P < 0.028) than that of the NP women (17.3 +/- 1.3%). The postpartum LACT and PPNL women had a reduced urinary excretion of calcium (P < 0.01) compared with the NP women. There was a significantly greater incorporation (P < 0.001) by LACT women of the oral isotope dose into milk than into urine. Calcium FA can be determined from incorporation of stable isotopes into breast milk and serum as well as urine.

Lactation decreases angiotensinogen mRNA expression in the midcaudal arcuate nucleus of the rat brain.

In lactating rats, ANG II receptor binding in the arcuate nucleus (ARH) and median eminence is decreased. To further evaluate brain angiotensinergic activity during lactation, we assessed angiotensinogen (AON) mRNA by in situ hybridization in forebrains of day 10 or 11 postpartum lactating and diestrous rats. AON mRNA was abundantly expressed in the ARH, preoptic, suprachiasmatic, supraoptic, paraventricular, and dorsomedial hypothalamic nuclei, and other regions, similar to that reported in male rat brains. AON mRNA levels were decreased 27% in the midcaudal ARH of lactating rats but did not differ between lactating or diestrous rats in any of the other brain areas examined. Immunofluorescence for AON and glial fibrillary acidic protein or tyrosine hydroxylase confirmed that the AON immunoreactivity in the ARH was limited to astrocytes. Confocal microscopy revealed close appositions of AON-positive astrocytes to dopaminergic neurons in the ARH. The decrease in AON mRNA in the midcaudal ARH during lactation coupled with decreased ARH ANG II receptor binding suggests that lactating rats are less subject to ANG II-mediated inhibition of prolactin secretion.

The effect of prepartum protein feeding on postpartum lactation performance of Ayrshire heifers and cows

The effect of prepartum protein feeding on postpartum lactation performance of Ayrshire heifers and cows

POPULATION DECLINE AND DELAYED RECOVERY IN BUNYORO, 1860–1960

RAPID population growth is commonly depicted as one of the greatest problems facing modern Africa. For decades, the tendency of birth rates to exceed mortality rates has prompted predictions of land shortage, resource depletion and mass starvation. Underlying causes of high fertility are hypothesized to have been an unusually high demand for human agricultural labour, ‘traditional religious pronatalism’ and a ‘horror of barrenness’, while in some areas the later colonial period saw a shortening of the durations of post-partum sexual abstinence and lactation. Mortality decline from the 1920s is commonly linked to the establishment of cash crop economies, networks of roads and railways, and the diffusion of western medicine, maternity facilities, missionary activity and primary education. Yet the empirical evidence supporting this model of population growth is contradictory. Areas such as Buhaya, Buganda and Bunyoro should have experienced rapid demographic expansion by natural increase in the colonial period according to dominant theories but instead experts in the early decades of this century feared the extinction of the Haya, Ganda and Nyoro. This paper will attempt to explain why population decline among the Nyoro was more severe than anywhere else in colonial Uganda, and probably East Africa.

Antibody responses in pregnancy-induced transmammary transmission of Ancylostoma caninum hookworm larvae

Third stage larvae of the Ancylostoma caninum hookworm nematode have the capacity to infect a dog, abort the normal maturation pathway to become blood-feeding intestinal worms, and instead distribute throughout the body in a developmentally arrested state that is relatively resilient to most chemotherapeutic agents. During pregnancy, a percentage of the arrested larvae reactivate and transmit via the mammary glands to infect the nursing puppies with resulting iron-deficiency anemia and potential mortality. To determine if the suppression of parasite-specific antibody responses during pregnancy facilitates the reactivation and transmammary transfer of hookworm larvae, a murine model of A. caninum infection was used to compare the infected versus uninfected animals that were either bred or not bred. Initial comparisons of genetically divergent BALB/c versus C57BL/6 mice showed that both the strains mounted strong Th2 biased IgG1and IgE antibody responses to A. caninum infection. Using the BALB/c strain for the breeding analyses, it was confirmed that larval transfer to the mouse pups only occurred during the post-partum lactational period. In the dams, levels of total and antigen-specific IgG1 and total IgE were highly correlated with parasite burden. During most phases of pregnancy and lactation, infected dams had lower total IgG1, IgG2a and IgE levels as compared to unbred mice at comparable times post-infection; this downward modulation of antibody responses supports the established dogma of a generalized immunosuppression associated with pregnancy. However, at parturition and post-partum lactation, antigen-specific IgG1 levels measured at 1 : 5000 serum dilutions were comparable between bred and unbred mice, and antigen-specific IgG2a levels at 1 : 100 serum dilutions were also not significantly different except for a marginal reduction in the bred mice at the lactational timepoint. The comparable anti- A. caninum IgG1 levels between bred and unbred mice, and low correlation between IgG2a levels and larval burden suggest that parasite-specific antibody responses do not play a major role in the pregnancy-associated transmammary transmission of A. caninum larvae. This conclusion does not rule out the possibility that underlying fluxes in the levels of specific cytokines associated with pregnancy and infection may be involved in the process of larval reactivation and transmission.

A comparison of women's memories of care during pregnancy, labour and delivery after stillbirth or live birth

Objective: to compare women's reports of aspects of their care during pregnancy, labour and delivery following stillbirth and live birth. Design: data were collected by postal questionnaire in 1994. Setting: a Swedish nation-wide population-based study of cohorts defined in 1991. Participants: three hundred and fourteen women with stillbirth (subjects) and 322 women with live birth (controls). Measurements and findings: labour and delivery were assessed as physically ‘insufferably hard’ by 52 (17%) of the subjects and 33 (10%) of the controls. The corresponding figures for emotional strains were 144 (47%) and 21 (7%). Obstetric analgesia was more frequently used during labour for stillbirth. One hundred and thirty-eight (44%) subjects, as compared to 44 (2%) of the controls, left hospital within 24 hours of birth. Almost all the women with stillbirth 296 (95%) stated that it was important to have an explanation of the baby's death. Adverse events related to bromocriptine given to inhibit postpartum lactation, were reported by 60 (22%) of the subjects. Key conclusions: it is possible to ease the distress of labour and delivery for stillbirth. Discussion of the aetiology of the baby's death with the mother should be a priority. The optimal length of stay in hospital after stillbirth remains to be defined. Non-pharmacological inhibition of lactation may be presented as an alternative to bromocriptine, breast binding is a concrete ‘reality confrontation’ for the woman and may aid her in her grieving process. Further studies concerning breast binding vs pharmacological inhibition of lactation and long-term psychological outcome are warranted.

Lactation increases prolactin receptor expression in spleen and thymus of rats

Prolactin receptors (PRL-R) are widely expressed on cells of the immune system. During lactation, the increase in serum PRL levels may modify the gene expression of these receptors. Specific PRL binding sites and the expressions of both PRL-R-L and PRL-R-S forms in thymus and spleen of nulliparous control, 10-day postpartum lactating, and 10-day postpartum nonlactating rats were studied. A semi-quantitative RT-PCR technique was used to detect the PRL-R gene transcript in the tissues. Our results showed that specific PRL binding sites and PRL-R-L mRNA and PRL-R-S mRNA were present in the lymphoid tissues with the PRL-R-L mRNA predominant. Lactation markedly increased specific binding sites and PRL-R-L mRNA in both spleen and thymus and only PRL-R-S in spleen. No differences between nulliparous control and postpartum nonlactating rats were observed in any of the parameters measured. The parallel increase in specific PRL binding sites and PRL-R-L mRNA suggests that lactation up-regulates PRL-R expression in lymphoid tissues and may be beneficial to the maternal immune system.

Expression of CSF-I and CSF-I receptor by normal lactating mammary epithelial cells.

Previous studies suggested a potential role for macrophage colony stimulating factor (CSF-1) in lactogenic differentiation of the breast. The aim of this study was to define the regulation of CSF-1 and its receptor (CSF-1R, the product of c-fms proto-oncogene) by lactogenic hormones in the breast in vivo during pregnancy and lactation and in vitro in organ culture and mammary epithelial cell lines. Immunohistochemical staining assays for the expression of CSF-1 and CSF-1R antigens were performed on sections of breast biopsies from nonpregnant (n = 10), prepartum (n = 4), and postpartum lactating patients (n = 7) and on sections of human mammary glands cultured in the presence of the lactogenic hormones insulin, prolactin, and glucocorticoids. Northern blot analyses were used to study the regulation of CSF-1 and CSF-1R by these same lactogenic hormones in normal and neoplastic mammary epithelial cell lines in cell culture. Normal, nonlactating mammary epithelium did not express CSF-1R and synthesized only low levels of CSF-1. During lactation, significant levels of both proteins could be observed in the epithelial cells that line actively lactating ducts and alveoli. Very similar increases in epithelial cell expression of CSF-1 and CSF-1R were observed in organ cultures of normal mammary gland biopsies exposed to prolactin, insulin, and glucocorticoids. Colony stimulating factor mRNA levels were increased by prolactin and/or insulin in a normal mammary epithelial cell line, while glucocorticoids had no apparent effect on CSF-1 mRNA levels. In contrast, we found that the levels of CSF-1R transcript are regulated primarily by glucocorticoids in breast carcinoma cells, while prolactin merely modulates the glucocorticoid effect. The observed increases in the expression of CSF-1 and its receptor during lactogenesis and the regulation of CSF-1/CSF-1R by lactogenic hormones suggests that this cytokine/receptor pair might play a regulatory role in the cellular events leading to the lactogenic differentiation of mammary epithelial cells.

Atrial natriuretic peptide and endothelin concentrations in human milk during postpartum lactation.

Milk samples from lactating women (n = 24) were examined for atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) content throughout the first 3 months postpartum. Samples were collected at the beginning (foremilk) and towards the end (hindmilk) of nursing. ANP was detected in the milk samples. A value of 9.4 +/- 1.8 pmol/l (mean +/- SEM) was observed on the third day postpartum. No significant variations in concentrations were observed during the 3 months examined. Foremilk and hindmilk ANP concentrations were also similar. ET-1, as previously reported, is present in the milk of lactating women. According to our observations, the concentration of ET-1 varies during the first 3 postpartum months. The highest concentrations were observed on the third day (10.2 +/- 1.8 pmol/l) of lactation, decreasing to 4.5 +/- 0.8 pmol/l after 1 week (p < 0.05) and to 2.0 +/- 0.3 pmol/l, at 1 month postpartum (p < 0.05), this level being maintained for up to 3 months postpartum. Foremilk samples on the third day postpartum contained significantly higher concentrations of ET-1, compared to hindmilk samples (10.2 +/- 1.8 vs 7.7 +/- 1.2 pmol/l, p < 0.05). The stable levels of ANP and the initial high and subsequently decreasing levels of ET-1 in human milk, during the first 3 months postpartum, suggest that these peptides might be of importance either in the lactating mammary gland or in the suckling newborn.

Two-follicle model for study of follicular waves in mares

This comparative study between postpartum lactating (PP Lactating) and non-postpartum cycling (N-PP Cycling) mares aimed to characterize reproductive patterns, types and frequencies of follicular waves, corpus luteum and endometrial echotexture dynamics, and the influence of season and body condition. Mares from each group were paired considering the day of parturition of a PP Lactating mare. The partum-ovulation interval (POI) and the postpartum interovulatory interval (PPIOI) were evaluated for PP Lactating mares, and 2 IOIs were evaluated for N-PP Cycling mares. The following observations were made: (i) PP Lactating mares have several different reproductive patterns, such as continuous reproductive activity (i.e., short or long POIs followed by a PPIOI), ovarian inactivity after the first postpartum ovulation, or continuous ovarian inactivity (postpartum anestrous phase); (ii) a greater total number of minor waves was seen in PP Lactating mares; (iii) major primary follicular waves (i.e., ovulatory) emerge around the day of parturition in mares with short POIs; (iv) the season of parturition (spring season), decrease in body condition score, and body-weight loss can have an associated detrimental effect in PP Lactating mares by increasing the total number of minor follicular waves and, consequently, the POI length; (v) endometrial echotexture scores are higher during the POI and can be influenced by the season of parturition; and (vi) corpus luteum development and demise are similar between PP Lactating and N-PP Cycling mares. This study provides, for the first time, detailed information about reproductive physiological aspects during the postpartum period and may facilitate the interpretation of gynecological practices during the foal heat and subsequent IOI in mares.

Central Retinal Vein Occlusion in a Woman Receiving Bromocriptine

We evaluated a unilateral retinal vascular abnormality in a 34-year-old woman receiving bromocriptine mesylate for the suppression of postpartum lactation. After using bromocriptine, 2.5 mg twice daily for 1 week, the patient complained of metamorphopsia in the left eye. A central retinal vein occlusion was found. We believe that central retinal vein occlusion in patients receiving bromocriptine, as demonstrated in our patient, is rare.

Plasma bovine placental lactogen concentration throughout pregnancy in the cow; relationship to stage of pregnancy, fetal mass, number and postpartum milk yield

This study characterized the peripheral plasma placental lactogen (bPL) profile throughout gestation and examined the relationship between the stage of gestation, fetal mass, number, and postpartum lactation with circulating levels of bPL in Holstein cows after nonsurgical embryo transfer. Cows (n = 12) were divided into two groups: Group 1 = single embryo recipient cows (n = 5); Group 2 = twin embryo recipient cows (n = 7). Blood was collected about every third day from Day 0 (Day 0 was defined as the first day of standing estrus), then daily for the last 10 d of gestation, and sampling was stopped 1 d postpartum. The cows were milked twice daily at 0800 and 1800 hr. Two twin-embryo recipient cows had abnormal pregnancies; therefore, their data were excluded from that of the group and reported separately. The time trend concentrations of plasma bPL were significantly affected by the stage of gestation (P < 0.01) but not fetal number (P < 0.21). In both groups bPL levels remained low during the first two trimesters, then increased rapidly (P < 0.01) to peak concentrations between Days 200 and 220, and stabilized at this elevated level until parturition. Postpartum milk yields were indistinguishable between the singleton and twin-bearing cows. Calf birth weight and postpartum lactation were both correlated (P < 0.01) to peripheral bPL concentration in singleton cows, however, this relationship decreased with a subsequent increase in fetal number. Cows giving birth prematurely to stillborn calves or to a schistosomus reflexus calf exhibited a deviating bPL profile. These results indicate that peripheral bPL levels are positively associated with the stage of gestation but not with fetal number. Otherwise, the peripheral pattern of bPL is a valuable index for predicting feto-placental viability.

Clinical Commentary: The Bromocriptine (Parlodel) Controversy and Recommendations for Lactation Suppression

Mounting concerns about bromocriptine (Parlodel) and rare cardiovascular and cerebrovascular accidents have prompted the manufacturer to remove the drug from the market for use in postpartum lactation suppression. No drug is available now or will be in the forseeable future for the indication. This change in prescribing practice should alert the physician to counseling the expectant mother about the merits of breast feeding and about simple, non-pharmacologic methods of suppressing milk production.

Bromocriptine and suppression of postpartum lactation. The incidence of adverse cardiovascular effects in women of child-bearing age.

The use of bromocriptine for the suppression of postpartum lactation drew widespread attention to a potentially increased risk for cardiovascular and cerebrovascular adverse effects. To estimate the incidence of these events a follow-up study was performed among 2,130 women of 15-44 years of age who were treated with a course of bromocriptine in 1990-1992. None of these women were admitted to the hospital for cardiovascular or cerebrovascular events. However, the incidence of pregnancy hypertension and the use of cardiovascular drugs increased considerably in the last 2 months before delivery. Therefore, cardiovascular or cerebrovascular events can probably be explained by pre-existing morbidity rather than by the use of bromocriptine. We estimated, using a 'worst-case' analysis, that fewer than 2 Dutch women each year would develop serious cardiovascular or cerebrovascular events.

A longitudinal study of urinary calcium, magnesium, and zinc excretion in lactating and nonlactating postpartum women

Postpartum lactating (n = 12) and nonlactating (n = 11) women and never pregnant women (n = 14) collected urine samples and diet records 2 d each month for 6 mo to determine whether postpartum women conserved urinary calcium, magnesium, or zinc. Mean daily excretions were analyzed by repeated-measures analysis of variance and covariance to assess group and time effects. Lactating women excreted less urinary calcium (1-6 mo) than never pregnant (n = 8) and nonlactating (n = 4) women who did not use oral contraceptives (P < 0.01); however, excretion rose (P < 0.05) by 3 mo postpartum. In the nonlactating and never pregnant groups, women using oral contraceptives excreted less urinary calcium than the other women (P < 0.01). Lactating women excreted less urinary zinc (1-6 mo) than did control and non-lactating women (P < 0.01). Mechanisms may possibly be operating during lactation that depress urinary calcium for > or = 2 mo and urinary zinc < or = 6 mo postpartum.

Stimulated thyrotropin and prolactin secretion in lactating and non-lactating women.

During the postpartum period, lactation is initiated by a massive release of prolactin which, in turn, reflects reduced dopaminergic inhibition of the pituitary lactotrophs. This postpartum prolactin rise can be prevented by administration of dopamine agonists. The release of thyrotropin (TSH) is also controlled by dopaminergic inputs and, therefore, TSH secretion may also be affected by postpartum alterations in dopaminergic activity. To gain further insight into the regulation of TSH and prolactin secretion during the postpartum period, we compared the basal and stimulated TSH and prolactin levels of postpartum lactating (n = 10) and non-lactating women (treated with 5 mg bromocriptine daily, n = 9) with those of normal cycling women (n = 9). Frequent blood samples were obtained on postpartum day 5 or in the early follicular phase before and after administration of thyrotropin-releasing hormone (TRH) for serial determination of TSH and prolactin by immunoradiometric assay (IRMA). Based serum prolactin levels were high (p < 0.001) in lactating women and low in both non-lactating and normal cycling women. When these differences in the basal prolactin concentrations were taken into account, the stimulated prolactin release (relative prolactin increase and area under the prolactin curve) was found to be highest (p < 0.05) in non-lactating women and lowest in lactating women. Basal TSH secretion was not significantly different between the groups of women (p > 0.2). Yet, both the relative TSH increases and the response curves following TRH stimulations were high (p < 0.05) in normal cycling women and low in both lactating and non-lactating postpartum women. These observations confirm a difference in the basal and stimulated prolactin release between lactating and non-lactating women. They also indicate that the TRH-stimulated TSH release is greatly affected by the postpartum state, irrespective of lactation or therapeutic weaning. The observation of a decreased sensitivity of pituitary thyrotrophs in concert with unchanged basal TSH secretion is suggestive of changes in hypothalamic TRH secretion and/or in the TSH metabolic half-life during the postpartum period.