Permissive effects of thyroid hormones on rat anterior pituitary mitotic activity

Abstract

The anterior pituitary is active mitotically and apoptotically under basal conditions and in response to a variety of physiological and pathophysiological stimuli. Hypothyroidism in man is associated with a modest but very occasionally dramatic increase in overall pituitary size. The mechanisms underlying this reversible phenomenon remain obscure. In the present study we have examined young adult rat anterior pituitary following surgical thyroidectomy and subsequent thyroid hormone treatment and withdrawal using an extremely accurate system for quantifying directly identified mitotic and apoptotic events. Despite the expected increase in the number and/or proportion of immunohistochemically identifiable thyrotrophs three weeks after thyroidectomy, mitotic and apoptotic activity remained unchanged, as did pituitary wet weight, in comparison with sham-operated and intact controls. In contrast, mitotic but not apoptotic activity was enhanced by treatment of thyroidectomized animals with thyroid hormones (triiodothyronine (T 3 ) and thyroxine (T 4 ) 1·8 µg and 3·6 µg/100 g body weight per day respectively), and once again declined to levels seen in intact animals within 72 h of subsequent thyroid hormone withdrawal. Thyroid hormone-induced enhancement of mitotic activity was also seen in intact rats treated with similar doses of thyroid hormones for 7 days and in thyroidectomized rats treated for a similar period with very low dose thyroid hormone replacement at a level that had no effect on raised hypothalamic TRH-or pituitary TSH -transcript prevalence (0·018 µg T 3 plus 0·036 µg T 4 /100 g body weight per day). Thus changes in mitotic and apoptotic activity are unlikely to be the principle mechanism for the apparent increase in thyrotrophs up to 4 weeks after thyroidectomy. In contrast, the data indicate that thyroid hormones have a permissive effect on anterior pituitary mitotic activity in thyroidectomized male rats. Thyroid hormone-induced enhancement of mitotic activity in intact rats further suggests that in euthyroid rats, ambient thyroid hormone levels are a limiting factor for anterior pituitary mitotic activity. In summary, this time course study of young, male rats has shown for the first time that thyroidectomy, thyroid hormone replacement and subsequent withdrawal has no significant effect on anterior pituitary apoptotic activity. Secondly, it has shown that the anterior pituitary mitotic response to thyroidectomy is blocked by complete thyroid hormone deprivation, but can be restored by very low level thyroid hormone replacement, and thirdly that in intact animals thyroid hormone levels significantly limit anterior pituitary mitotic activity.

Prolonged oestrogen treatment does not correlate with a sustained increase in anterior pituitary mitotic index in ovariectomized Wistar rats

“…However, the pars distalis is not only mitotically active under basal conditions but has been shown to be highly responsive to changes in ambient glucocorticoid, male hormone and thyroid hormone levels (Nolan et al . 1998, 1999, 2004). Several studies have also been sensitive enough to suggest a diurnal variation in mitotic activity in the pituitary, although there is some disagreement about the exact number and timing of peak/s and nadirs (Nouet & Kujas 1975, Carbajo-Perez & Watanabe 1990, Carbajo-Perez et al .…”

“…Pituitary sections were processed for BrdU immunohistochemistry according to a previously published protocol (Cameron & McKay 1999) with minor modifications (Nolan et al . 2004).…”

A Population of Non‐Luteinising Hormone/Non‐Adrenocorticotrophic Hormone‐Positive Cells in the Male Rat Anterior Pituitary Responds Mitotically to Both Gonadectomy and Adrenalectomy

“…Standard pituitary tissue sections for trophic analysis and immunohistochemistry were prepared exactly as described (4). Pituitary sections were processed for BrdU immunohistochemistry according to a previously published protocol (6) with minor modifications (7), and subsequently for either ACTH or LH using rabbit polyclonal anti‐ACTH or anti‐LH antibodies (NIDDK kindly provided by Dr A. F. Parlow; diluted 1 : 2000 in blocking serum), biotinylated anti‐rabbit IgG (Vector Laboratories, Peterborough, UK; diluted 1 : 200 in blocking serum) and R.T.U. Vectastain Elite ABC reagent according to the manufacturer's instructions (SK‐4600; Vector Laboratories).…”

The effects of testosterone and oestrogen on gonadectomised and intact male rat anterior pituitary mitotic and apoptotic activity

“…mitotic and apoptotic) activity, in the present study we have carefully examined the responses of the rat anterior pituitary to surgical gonadectomy and various sex hormone treatments over a period of 4 weeks. To do this we have used a well-validated manual, but computer-assisted, image analysis system to quantify directly identified mitotic and apoptotic events in thin haematoxylin-and eosin-stained anterior pituitary sections (Nolan & Levy 2001, Nolan et al 2004a, 2004b. The data have allowed us to build a more complete portfolio of understanding of trophic influences on the male rat pituitary (Levy 2002).…”